• 

  ON-OFF Pathway Function in Amblyopia

  Kuznia, Jon (2025)

  "Purpose To understand the effect of amblyopia on ON and OFF pathway asymmetries. This pilot study used a novel, eye-tracking, saccadic-based perimetric test. Methods 8 eyes of 4 amblyopic subjects (mean age 24 ± 2.4 years) and one eye of 4 age-matched control subjects (mean age: 27 ± 3.6 years) were tested using a novel perimetric test. We tested 4 Michelson contrast levels ranging from 15 to 5% at 3 annular eccentricities: 5- 10, 11-20, 21-30 degrees from fixation (2.5-degree radius circle). Each contrast level was comprised of 579 trials. Each test location was repeated 3 times for both light and dark stimuli, with 6 repeats in each of two blind spot positions. Stimuli, light or dark squares which varied in size as a function of eccentricity, were presented on a binary noise background. The angular difference between the target location and eye position following a saccadic movement to the target location and reaction time were measured for every trial. Percentage of undetected targets, the angular difference between the target location and eye position following a saccadic movement to the target location, and reaction time were measured for every trial. Hardware consisted of a head mounted display equipped with an eye tracker (HTC VIVE embedded Tobii) with a refresh rate of 90 Hz, a max luminance of 110 cd/m2, and a horizontal field of view of 60 degrees. Unity (version 2017) software was used to generate the stimuli. Results At low contrasts (less than 10%), the amblyopic eyes of patients have a greater percent error rate (12.12 ± 17.56 %, p = 3.2 x 10-17, Wilcoxon tests for all statistical comparisons), detect fewer targets (6.98 ± 16.28 %, p = 8.5 x 10-8) and have longer reaction times (101.2 ± 193.8 msec, p = 1.13 x 10-11) when compared to fellow eyes. However, the fellow eyes of amblyopic subjects have greater percent error rate (8.03 ± 8.64 %, p = 0.0013), detect fewer targets (8.68 ± 7.2 %, p = 2.9 x 10-4) and have similar reaction times (29.8 ± 110.6 msec, p = 0.811) to the control subjects. At a low contrast (6%), the difference between amblyopic and fellow eyes across eccentricities was significantly larger for light than dark stimuli in percentage of errors (5.37 ± 10.43%, p = 0.031), undetected targets (4.91 ± 6.5%, p = 0.001) and reaction time (44.2 ± 96.7 msec, p=0.026). This difference was not apparent at 5% contrast due to the high rate of errors for both light and dark stimuli. Conclusion These results provide further support to previous work indicating that amblyopia affects ON more than OFF pathways. However, given our very limited sample size, further evaluation is necessary. The use of the perimetric test in this study, along with continuing advancements, may enable this work to continue in a clinical setting."
• 

  Effects of Induced Myopia on Inner Peripapillary Retinal Layer Structures

  Song, Brian (2025)

  "Purpose: Myopic eye growth exerts mechanical stretching that can reshape the retinal architecture. This study investigates the longitudinal impact of induced myopia on peripapillary retinal layer structures in the common marmoset (Callithrix jacchus), a non-human primate model with close anatomical and developmental similarities to the human eye. Methods: Thirteen juvenile marmosets were reared under binocular negative lens defocus for 23 weeks to induce myopia (six controls and seven treated). Serial measurements of cycloplegic refractive error and vitreous chamber depth were conducted alongside spectral domain optical coherence tomography (SD-OCT) imaging to assess regional peripapillary retinal layer thickness. Segmentation of OCT scans were used to quantify changes in total and individual retinal layers across four quadrants. Results: Control animals exhibited age-related peripapillary thickening, particularly in the temporal quadrant of multiple inner retinal layers. In contrast, myopic eyes showed reduced thickening, and thinning at times, especially in the inferior and temporal regions. In particular, a significant thinning was observed in the inferior quadrants of the ganglion cell and inner plexiform layer in treated eyes. A regression analysis identified the inferior total retinal thickness and ganglion cell layer thickness to be the strongest predictors of vitreous chamber depth. Conclusions: Induced myopia in marmosets leads to regional thinning of inner peripapillary retinal layers, suggesting early remodeling due to asymmetric retinal expansion. These findings contribute to understanding structural biomarkers of myopic progression and support the use of the marmoset model in translational vision science research."
• 

  ANALYSIS OF GLIA CHARACTERISTICS IN THE RD10 RETINITIS PIGMENTOSA MOUSE IN COMPARISON TO THE MÜLLER GLIA DICER-CKO MOUSE, TWO MODELS OF RETINAL DEGENERATION

  Rief, Alexander Marian (2025)

  "Purpose The retinal degeneration (RD) 10 mouse is a well-studied animal model that develops Retinitis Pigmentosa (RP) due to a mutation in rod photoreceptors. Müller glia (MG) are the predominant glia in the retina, have essential roles in the healthy retina, but become reactive in response to retinal damage and contribute to secondary neuronal loss. An in-depth characterization of MG in the RD mouse has not reported yet. Furthermore, molecular alterations in MG, i.e., the depletion of the enzyme Dicer1, results in photoreceptor loss resembling the phenotype of RP. Therefore, similarities in the molecular profile of MG in both models could suggest a putative common regulatory mechanism of glial alteration. The aim of this study was to characterize and compare MG in the central and peripheral retina in the RD10 mouse and the MG-specific Dicer1 conditional knock-out mouse. Methods To visualize MG in both degeneration models a MG-specific reporter mouse (Rlbp1-CreER:tdTomatostop flox/flox) was crossed with the RD10 or the Dicerflox/flox mouse (Dicer knock-out, referred to as cKO). Histological analysis was performed by means of immunofluorescence staining and confocal microscopy imaging. Retinal cross sections of 1-, 3-, and 6-months old mice were evaluated with regard to overall retinal histology, MG number and their glial protein expression pattern in both the center and periphery. Results The RD10 mouse displayed retinal thinning as early as one month of age with proliferating MG at the early phase and degenerating MG at later phases. These MG were glial fibrillary acidic protein (GFAP) positive and vimentin positive at all time points analyzed. The Dicer-cKO mouse displayed proliferating MG at early stages but not obvious degeneration was found at this time. At later stages, MG number declined in central retinal areas which were also significantly degenerated. GFAP and vimentin upregulation was not found in Dicer-cKO MG. Conclusion The MG reporter mouse is a very useful tool to study MG number and behavior in models of retinal degeneration including the RD10 mouse and the Dicer-cKO mouse. Moreover, it appears that the deletion of Dicer1 prevents MG from becoming reactive and initiating gliosis. This suggests that molecular manipulation of MG could be utilized to attenuate gliosis and subsequent degenerative events in retinal diseases."
• Uncorrected Myopia Affects the Visual Resolution of OFF Pathways More Than ON Pathways

  Chen, Xiao Tong (2025)

  "Introduction: The balance between ON- and OFF-pathway responses is believed to play a significant role in the progression of myopia in children [1, 2]. In a recent study, we found that uncorrected myopic children exhibited poorer visual acuity—approximately 1.5 logMAR lines—when identifying dark optotype stimuli (primarily processed by the OFF-pathway) compared to light stimuli (processed by the ON-pathway). In this study, we examine whether this asymmetry between light and dark stimuli is associated with the severity of myopia. Methods: Cycloplegic refractive error was used to calculate the spherical equivalent (SEQ). Based on SEQ, children aged 8 to 12 years were divided into two groups: a myopic group (−0.75D to −6.00D, N=11) and a non-myopic control group (−0.38D to +1.25D, N=15). Corrected and uncorrected right eye visual acuity (VA) was assessed using E-ETDRS charts with either light or dark optotypes presented at full contrast (on dark or light backgrounds, respectively) in randomized order, repeated twice with a 30-minute interval. Light-dark asymmetry was quantified using the ON-OFF VA ratio. Results: The myopic group demonstrated significantly greater light-dark asymmetry compared to the control group (1.15 ± 0.08 vs. 1.00 ± 0.02, p < 0.001), indicating that uncorrected myopic eyes experience increased difficulty in resolving dark optotypes relative to light ones. Furthermore, a modest yet statistically significant correlation was observed between spherical equivalent (SEQ) and the ON-OFF visual acuity ratio (r = 0.38; t = −2.4, p = 0.02), suggesting that this asymmetry becomes more pronounced with increasing severity of myopia. Conclusions: These findings suggest that uncorrected myopic eyes have more difficulty perceiving dark compared to light stimuli, and that this ON-OFF pathway imbalance is associated with the degree of myopia. Further research is warranted to explore the potential of light-dark asymmetry as a biomarker for monitoring myopia progression in children."
• 

  Differences between ON and OFF cortical function in patients with amblyopia

  Nguyen, Vanna Lam Vy (2025)

  "Purpose: Evidence from psychophysical studies indicate that amblyopia affects ON more than OFF visual pathways. This prospective study aims to directly measure the effect of amblyopia on cortical responses driven by ON and OFF pathways with visual evoked potentials (VEPs). Methods: Adults (18-65 years) with amblyopia (strabismic, anisometropic, mixed, or deprivational) and control subjects with binocularly normal-corrected vision were recruited. All subjects were screened with ATS-EDTRS best-corrected visual acuity (BCVA) and Randot Preschool stereoacuity. To be eligible, amblyopes must have an interocular difference of ≥2 logMAR (logarithmic minimum angle of resolution) lines, and controls must have BCVA within 1 logMAR line in both eyes and a stereoacuity of ≤100 arcsec. VEP was recorded with a portable lightweight headset (Wearable Sensing Inc.) that sampled the visual cortex with 9 dry electrodes. The visual stimuli presented were checkerboards with half checks equal to the background and half darker or lighter than the background (100% and 50% contrast, viewed through right eye, left eye, or both eyes, 900 trials). Eye fixation was monitored with an eye tracker (Eyelink 1000). The reliability of cortical responses was quantified with a correlation index that selected the 20 stimulus trials generating the strongest responses and measured the average of all possible correlations between trial pairs. Results: We tested eight amblyopic subjects and two controls. The average amplitude of the cortical responses was marginally stronger for the AE than FE, but the difference was not statistically significant (23.00 ± 4.65 vs. 22.68 ± 5.62 microV, p > 0.05, Wilcoxon test). Differences in response amplitude between FE and AE were weaker for light than dark stimuli but also did not reach significance (-0.38 ± 4.81 vs. -0.26 ± 7.22 microV, p > 0.05, Wilcoxon test). The mean correlation index was larger in the FE than the AE, but this difference was not statistically significant (0.43 ± 0.20 vs. 0.40 ± 0.22, p > 0.05, Wilcoxon test). The FE-AE differences in mean correlation index were larger for light than dark stimuli, but again, the differences did not reach significance (0.09 ± 0.20 vs. -0.03 ± 0.22, p > 0.05, Wilcoxon Test). Within-subject comparisons in select individuals revealed variable VEP patterns. Control subjects showed no interocular or ON/OFF differences, while amblyopic participants displayed mixed results. Some were consistent with the hypothesis of reduced ON pathway strength in the AE, whereas others showed the opposite or no difference at all. Conclusion: While some amblyopes may show ON/OFF pathway asymmetries, these effects are not consistently observable across all cases. Variability is inherent with VEP and may limit the ability to detect ON/OFF pathway differences at the group level, emphasizing the need for individualized analysis in amblyopia research."
• 

  The Effect of Biofeedback Training on Accommodation During MFCL Wear in Young Adults

  Patel, Sweta (2025)

  "Purpose: Myopia currently affects 22.9% of the global population and it is estimated that 50% of the world population will be myopia by 2050. Multifocal contact lenses (MFCLs) are effective in reducing myopia progression, but with variable efficacies. One potential reason could be reduced accommodation through the MFCLs. This is due to the near add in the MFCLs superimposing peripheral myopic defocus or reducing peripheral hyperopic defocus, which then leads to a relaxation of accommodation. The drawback, however, is that if myopes reduce accommodation when reading through the MFCLs, it may reduce peripheral myopic defocus and ultimately, reduce the treatment effect of MFCLs. Recent studies show that auditory biofeedback training can help improve accommodation through the MFCLs in young myopes both immediately after the training and one week later, which may ultimately improve the efficacy of MFCLs. In this study, we evaluated, in young adults, the time course of biofeedback training in increasing accommodative response during MFCL wear and if weekly repetition of the biofeedback training and increased training duration could lead to longer lasting results. Methods: This was a prospective study with 4 weekly visits. Twenty-seven young myopes with normal accommodation and binocularity were fit with Biofinity single vision (SV) and MF (+2.00 Add center distance) CLs over both eyes and randomized to 3 groups: (1) Group 1 – single training, (2) Group 2 – regular repeated training, and (3) Group 3 – extended repeated training. During Visit 1 for all 3 groups, accommodation was measured first through the SVCLs, then through the MFCLs before and after an auditory biofeedback training at four different dioptric distances: 2.5D, 3D, and 4D. During Visits 2 and 3 for group 1, accommodation through the MFCLs was measured without the biofeedback training. During Visits 2 and 3 for group 2, accommodation was measured before and after auditory biofeedback training. During Visits 2 and 3 for group 3, accommodation was measured before and after an extended auditory biofeedback training (twice the duration). Visit 4 for all groups consisted of measuring accommodation through the MFCLs without auditory biofeedback training. Results: Analysis of the data confirmed that accommodative responses were reduced in MFCLs compared to SVCLs. One session of auditory biofeedback training was also shown to increase the accommodative responses in MFCLs at the 2.5 D, 3 D, and 4D distances and the effect of the training lasted for at least one week as supported from the data pooled together of all subjects. In subjects who received the training in the first session, effects of the training lasted for the entire month. However, increasing the number of trainings (as performed for Group 2 subjects) or the duration of the training (as performed for Group 3 subjects) did not significantly further increase the efficacy of the biofeedback training. Conclusion: Biofeedback training could potentially be used as an adjunct treatment for slowing down myopia progression when coupled with MFCL wear. Since one training of auditory biofeedback training showed success in increasing accommodative responses, it may be worthwhile to determine what changes can be made in the execution of the training to yield the best results. While this study was performed on young adults, future directions may include performing a similar study design on myopic children due to the greater accommodative capabilities of children in comparison to adults. "
• 

  microRNAs in Retinal Development and Müller glia Reprogramming

  Kang, Seoyoung (2025)

  "Retinal diseases lead to visual impairments with loss of neurons and often cause blindness. Since the mammalian retina has no regenerative capability, one of attractive strategies is cell replacement, achieved by reprogramming endogenous mature cells. There are attractive molecules that regulate gene expression and are elementary during retinal development (retinogenesis), and also can induce reprogramming in mouse Müller glia (MG). MG, predominant glia in the retina, are known to have regenerative capacity naturally in fish, unlike mammalian. Recent studies demonstrated that microRNAs (miRNAs) play an important role in the embryonic phase of retinogenesis, and the set of miRNAs can induce mouse MG reprogramming into neuronal-like cells that express neuronal markers and have neuronal morphologies. The miRNAs were, however, poorly understood in the postnatal processes of retinogenesis. Furthermore, the questions include which cell types can be generated and, most importantly whether these neuronal cells are mature and functional were not answered yet. Therefore, the aims of this study were to 1) analyze the effects of loss of miRNAs in the late retinal progenitor cells (RPCs) during postnatal retinal development, to 2) evaluate the reprogramming efficiency of the RPC-miRNA miR-25 with regard to the generation of functional neurons. Aim 2 included the establishment of an improved cell culture protocol together with calcium imaging in order to investigate the functionality and maturation state of these newly generated neuronal-like cells. Aims one and two included the establishment of luciferase reporter assays to identify a possible underlying mechanism. Loss of miRNAs in late RPCs is caused by a genetic knock-out of the enzyme Dicer, required for the formation of mature, functional miRNA and Ascl1CreER:tdTomato strain (RPC reporter mouse). The tissue was examined at different timepoints and evaluated histologically. For MG reprogramming, RPC-miRNA miR-25 was overexpressed using artificially made miRNAs called mimics, in mouse primary MG. Cells were monitored and evaluated over the time course of three weeks. miRNA target gene analyses were performed to identify potential underlying mechanisms. Our data showed that loss of miRNAs in late RPC reduced populations of bipolar cells, rod photoreceptors, MG and increased an amacrine cell population. We found that miR-25 directly target amacrine cell mRNAs, Elavl3, a gene that encodes for HuC, a protein expressed in amacrine cells. Using the RPC-miRNA miR-25 to reprogram young primary MG led to a conversion of the cells to more immature cells. We show for the first time that one miRNA alone, namely miR-25, was sufficient to successfully reprogram primary MG into progenitor cells that subsequently differentiate into functional neurons. This cell conversion might be partly due to the inhibition of the neuronal repressor Rest, a direct target of miR-25. Furthermore, we found that miRNA molecules were taken up efficiently by all glia, however, not all glia were reprogrammed. This suggests that the competence state of the glia might play a role in reprogramming. Taken together, late RPC-miRNAs are essential for the proper development of late-born cells and miRNA loss leads to reduced bipolar cells, photoreceptors, and MG populations but an increase in amacrine cells. The reduced bipolar cell number might be partly due to a competent shift of the progenitors towards amacrine cell generation. Furthermore, the RPC-miRNA miR-25 alone is sufficient to successfully reprogram primary MG into progenitor cells that subsequently differentiate into functional neurons. The neuronal repressor Rest might be one of the primary key players in this process. Since miRNA molecules were taken up efficiently, remained at least 4 weeks after transfection, and no toxicity was detected, miR-25 might be a promising tool for in vivo MG reprogramming. "
• 

  Investigating a Link Between Visual Function and Menstruation

  Goodwin, Emma (2025)

  "Throughout the course of a normal menstrual cycle, a woman’s hormone levels vary greatly and these changes cause the body to react in a multitude of ways. However, there is little previous research remarking on the link between visual function and the menstrual hormones. The objective of this study was to determine how visual function is impacted at different stages in the menstrual cycle. Specifically, tests of high and low contrast visual acuity, lag of accommodation, color vision, and critical flicker fusion frequency were recorded in order to examine changes in visual function over a normal menstrual cycle. This study recruited all subjects from the SUNY College of Optometry as well as the areas surrounding the school between the ages of 18-30 years old. 12 female subjects not currently pregnant or on birth control medication as well as 3 male control subjects will participate. Subjects performed the required clinical measurements 5 days a week for 5 weeks (25 total days) to encompass the entire menstrual cycle. In addition, female subjects also reported the day of their last menstrual cycle and any other perceived changes in visual function throughout the month. No significant difference was found between the female and male groups or within the female group throughout the month for any parameter tested. Further parameters should be measured in the future in order to gain a clear image of how menstruation impacts the whole ocular system."
• 

  ON-Pathway Visual Acuity Deficits in 8-12 Years Old Children with Unilateral Amblyopia

  Li, Jerry (2025)

  "Purpose: Conventional recognition visual acuity (VA) tests, using black optotypes on white background, do not detect ON-pathway amblyopia deficits. This pilot study tests the hypothesis that VA testing with white optotypes on black background is more sensitive in detecting amblyopia than with black optotypes on white background. Methods: Two groups of children aged 8-12 were enrolled. The amblyopic group (N=13) had a best-corrected VA of 20/32 or worse in the amblyopic eye and an interocular VA difference of ≥0.2 logMAR. The control group (N=16) had best-corrected VA equal to or better than 20/25 and had an interocular VA difference of ≤0.1 logMAR. Participants’ VA were tested monocularly with an ETDRS program using the Amblyopia Treatment Study protocol and reported as a Score. Two optotype polarities were randomized, and tests were repeated after 30 minutes. VA in Scores were compared between amblyopic, fellow, and control eyes for both polarities. Results: For amblyopic eyes, the mean VA Score was significantly lower for white than for black optotypes (57.85±10.72 vs 61.46±10.10, p<0.001), indicating that amblyopic eyes had more difficulty seeing white than black optotypes. For fellow eyes, the mean Score was marginally significantly lower for white than for black optotypes (85.77±3.23 vs 87.73±4.61, p=0.03). No significant differences were found in control eyes (87.70±3.38 vs 88.02±4.03, p=0.63). Conclusions: VA in amblyopic eyes is 3.6 letters (~0.07 logMAR) worse when measured with white optotypes than black optotypes, indicating that white optotypes have higher sensitivity in detecting amblyopia ON-pathway deficit."
• The effects of glare, luminance and contrast on visual acuity (VA)

  Arun, Geerdhana (2025)

  "Purpose: Clinical measurements of VA are typically obtained under optimal conditions using high contrast optotypes. However, these conditions are not representative of real-life environments where observers are frequently faced with low contrast, low luminance targets accompanied by significant degrees of glare. Accordingly, the aim of the present study was to measure VA under both optimal and suboptimal conditions in younger and older adults. Method: The study was performed on 30 older (ages 50-71 years) and 30 younger (21-28 years) subjects. High (0.0 log unit) and low (1.05 log unit) contrast VAs were tested using the Adhikari Carter Feigl Zele logMAR chart. VA was measured both with and without a 0.3 neutral density (ND) filter to create low luminance conditions, as well as both with and without an LED glare source being directed into the eye. Results: The average change in VA under the low contrast and low luminance conditions were 1.22 logMAR (p < 0.001) and 0.94 (p < 0.001), respectively. Average VA changed by -0.77 in the presence of glare (p < 0.001). There were no significant age effects noted between the two groups (p=0.25). Interaction effects were significant between luminance and contrast (p < 0.001) as well as between luminance, contrast and the presence of glare (p < 0.001) in both age groups. Conclusions: The results demonstrate that reducing contrast and luminance produced a significant decline in VA in younger and older adults. This finding has considerable clinical significance, for example when driving at night, where a subject with excellent VA in the examination room might exhibit very poor VA under degraded conditions. Clinical measurements should include assessment of visual performance under sub-optimal conditions. "
• 

  Helping Our Graduate Students SOAR: Promoting Scholarship and Populating Our Institutional Repository

  Wells, Elaine (East Tennessee State University Charles C. Sherrod Library, 2024-11-18)

  The author describes how a requirement that our graduate students deposit theses and dissertations into our institutional repository (SOAR) helped to build our online scholarship, educate and strengthen graduate stu- dents’ identities as scholars, and forge relationships with the library. Taking advantage of the synergy brought about by a new open access policy, a robust digital repository, and library staff committed to advancing accessible scholarly works, we developed ways to educate, encourage, and promote our newest scholars. Based upon our success thus far, we will develop workshops and tutorials that will be extended to junior faculty to advance their scholarly success.
• Functional contributions of ON and OFF pathways to human vision

  Poudel, Sabina (2024)

  "The human visual system processes light and dark stimuli with separate ON and OFF neuronal pathways that originate in the retina, at the first synapse of the visual system, and remain segregated in the rest of the brain. In animal models, ON and OFF pathways are differently modulated by the spatiotemporal properties of stimuli. In my thesis, I investigate the stimulus modulations of these two pathways in humans and the possible clinical implications of their functional differences. In the first chapter, I record visual images and visuomotor activity in human subjects performing two visual tasks, reading and walking indoors, while wearing Tobii Pro Glasses 2. Reading and walking are known to pose different risks of myopia progression, a visual disorder that blurs vision at far distances. However, the stimulus parameters driving myopia progression remain unclear. To investigate this question, I quantify the visual input to the retina and visuomotor activity during the two tasks. I demonstrate pronounced task differences in the stimulation balance of ON and OFF visual pathways. My results demonstrate that reading reduces central visual stimulation of ON visual pathways and decreases visuomotor activity and reflexes dominated by ON visual pathways. These results support the hypothesis that reading drives myopia progression by under-stimulating ON visual pathways. In the second chapter, I use electroretinography (ERG) to measure the contrast response functions of ON and OFF retinal pathways in humans and further investigate if the two pathways are differently affected by myopia. We have previously demonstrated that ON and OFF pathways have different contrast sensitivity in visual cortex, and that the difference increases with luminance range (defined as the difference between maximum and minimum luminance in an image). Here, I demonstrate that these ON-OFF differences are already present in the human retina and are affected by myopia. I show that myopia is associated with a deficit in ON retinal pathway function that reduces the retinal ability at signaling low contrast and regulating retinal illuminance in bright environments. In the third chapter, I measure spatial frequency tuning of retinal ON and OFF pathways in humans using pattern ERG. Previous studies from our lab demonstrated that, in carnivores and non-human primates, ON and OFF cortical pathways have different spatial frequency tuning. My results demonstrate that these ON-OFF tuning differences are also present in the human retina. I show that retinal responses to light stimuli are tuned to higher spatial frequencies than retinal responses to dark stimuli. High spatial frequencies drive stronger responses from retinal ON pathways whereas low spatial frequencies drive stronger responses from retinal OFF pathways. Overall, my results reveal new insights on the function of ON and OFF retinal pathways in humans, and add to the growing research effort to understand the link between retinal circuitry and myopia. My research may also help to explain why outdoor activity and reading have opposite effects on myopia progression, and lead to novel approaches for myopia control. "
• 

  Neuronal properties, neural populations, and mental geometry in inferring object attributes

  Maruya, Akihito (2024)

  "In the first chapter, we reveal that while many studies have focused on size invariance concerning physical distance, the constancy or inconstancy of relative size with respect to object pose has been largely overlooked. Our findings demonstrate a systematic underestimation of length for objects oriented toward or away from the observer, whether static or dynamically rotating. While observers attempt to correct for projected shortening using the optimal back- transform, these corrections often fall short, particularly for longer objects that appear more slanted. Incorporating a multiplicative factor for perceived slant into the back-transform model yields a better fit to the observed corrections. In the second chapter, we extend this investigation to obliquely viewed pictures, comparing human performance to the optimal geometric solution. We show that size and shape distortions occur in oblique views, particularly for objects at fronto-parallel poses, leading to significant underestimation. We found that empirical correction functions, although similar in shape to the optimal, are of lower amplitude, likely due to systematic underestimation of viewing azimuth. By adjusting the geometrical back-transform to account for this bias, we achieve better fits to the estimated 3D lengths from oblique views. These results add to the evidence that humans use internalized projective geometry to perceive sizes, shapes, and poses in both real scenes and their photographic representations. The third chapter addresses the perception of rigidity and non-rigidity in rigidly moving objects. We used rotating rigid objects that could appear either rigid or non-rigid to test the contribution of shape features to rigidity perception. Our results show that salient features such as gaps or vertices reinforce the perception of rigidity at slow and moderate speeds, while all configurations appear non-rigid at high speeds. We also demonstrate that motion flow vectors from local ME computation are predominantly orthogonal to the contours of the rings rather than parallel to the rotation direction. A convolutional neural network trained to distinguish flow patterns for wobbling versus rotation showed that motion-energy flows contribute to the perception of wobbling, while feature tracking mechanisms enhance the perception of rotation. Interestingly, circular rings can sometimes appear to spin and roll even without any sensory evidence, an illusion that is mitigated by the presence of vertices, gaps, and painted segments, highlighting the role of rotational symmetry and shape. By combining CNN outputs that prioritize motion energy at high speeds and feature tracking at low speeds, along with shape-based priors for wobbling and rolling, we were able to accurately explain both rigid and non-rigid perceptions across different shapes and speeds (R2=0.95). These findings demonstrate how the cooperation and competition between different classes of neurons lead to distinct states of visual perception and transitions between those states. Finally, the fourth chapter investigates the anisotropy in object non-rigidity, linking it to low-level neural properties in the primary visual cortex. By combining mathematical derivations and computational simulations, we replicate psychophysical findings on non-rigidity perception in rotating objects. Our analysis reveals that perceived shape changes, such as elongation or narrowing of rings, can be decoded from V1 outputs by considering anisotropies in orientation-selective cells. We empirically show that even when vertically rotating ellipses are widened or horizontally rotating ellipses are elongated to match shapes, the perceived difference in non-rigidity decreases, but heightened non- rigidity remains in vertical rotations. By integrating cortical anisotropies into motion flow calculations, we observed that motion gradients for vertical rotations align more closely with physical wobbling, whereas horizontal rotations fall somewhere between wobbling and rigid rotation. This indicates that intrinsic cortical anisotropies play a role in amplifying the perception of non-rigidity when orientation changes from horizontal to vertical. The study highlights the significance of these cortical anisotropies in influencing perceptual outcomes and prompts further exploration of their evolutionary purpose, particularly in relation to shape constancy and motion perception.
• 

  Myopia's Influence on the Retinal Neurovascular Unit and its Implications in Glaucoma

  Lin, Carol (2024-08)

  "Myopia is an increasingly common refractive error that not only causes distance vision blur, but also poses greater risks of developing ocular pathologies such as choroidal neovascularization, retinal detachments, glaucoma, and various maculopathies1, 2. Myopia prevalence is projected to increase from 28% in 2010 to almost 50% by 2050, and affect almost 5 billion people around the world3, 4. The global myopia epidemic is impossible to deny or ignore, with myopic maculopathies the primary cause of irreversible vision loss worldwide3. Glaucoma is a multifactorial eye disease characterized by irreversible optic neuropathy, progressive visual field deficits, and occasionally intraocular pressure (IOP) elevation; it is the second leading cause of blindness worldwide, and is estimated to affect over 120 million people by the year 20405. There is strong evidence confirming a relationship between myopia and glaucoma, and that myopic patients are more susceptible to glaucomatous degeneration. However, the mechanisms fundamental to this association remain unknown. There exist no early diagnostic markers for preventing myopia-associated glaucomatous onset and development1, 2, which can cause irrevocable structural and functional deficits, subsequently increasing vulnerability of the retina to glaucomatous degeneration. Through the work completed in this thesis, an assessment of components of the retinal neurovascular unit was performed to elucidate the effect of sustained myopia in an experimental non-human primate (NHP) model, and how myopia predisposes the retina to glaucomatous damage due to the effects of myopic eye growth and stretch on the inner retina. Myopia was induced in marmosets using soft single vision contact lens wear of varying refractive errors, while glaucoma was induced via intracameral injection of microbeads, causing angle occlusion and IOP elevation. Successful marmoset models of myopia, glaucoma, and myopic glaucoma were generated. During treatment, measurements of individual retinal layer thicknesses, axial length, and refractive error were gathered, and the density and distribution of retinal ganglion cells, astrocytes, and vasculature via immunohistochemistry (IHC), retinal layer thicknesses via optical coherence tomography (OCT), and functional assessment of cell function via electroretinography (ERG) were performed. Aim 1 investigated the effect of myopia on the retinal vascular template, astrocyte template, and retinal nerve fiber layer (RNFL) thickness in 6-month-old marmosets induced with myopia for four months. The analysis revealed an increase in pan-retinal string vessels and a decrease in peripheral vascular branch points, a decrease in Sox9+ astrocyte density, and increased glial fibrillary acidic protein (GFAP) glial reactivity in myopic eyes compared to age-matched controls. The RNFL was also thinner in myopic eyes compared to age-matched controls, and the relationship between astrocyte density and RNFL thickness known to exist in primates was present in controls, but not in myopic eyes. Aim 2 explored the effect of sustained defocus and aging on the retinal microvascular template of marmosets induced with myopia for four months compared to marmosets induced with myopia for ten months and age-matched controls. The analysis revealed an increased number of string vessels in all four vascular plexi and increased vascular branch points in the parafoveal retina but decreased in the peripapillary and peripheral retinas with myopia progression. Aim 3 examined the effect of sustained myopic eye growth on astrocyte cellular distribution, and its association with inner retinal layer thicknesses in marmosets induced with myopia for 4 months compared to marmosets induced with myopia for 10 months and age-matched controls. Myopic marmosets induced for 10 months experienced exacerbated pan-retinal decreased astrocyte density and increased GFAP-immunopositive spatial coverage, similar RNFL thinning but greater"
• 

  Digital eye strain and pupillary response to blue light

  Ng, Derek (2024)

  "Purpose: Digital eye strain (DES), a multifactorial condition affecting millions worldwide, often implicates blue light as a contributing factor. While blue light blocking filters are marketed to alleviate DES symptoms, evidence supporting their efficacy remains limited. Intrinsically photosensitive retinal ganglion cells (ipRGCs), exhibiting peak sensitivity to blue light, are involved in regulating pupil constriction and circadian rhythms. Notably, blue light elicits varying ipRGC-mediated pupil responses between individuals. This study investigated a potential association between self-reported DES symptoms and individuals' ipRGC-mediated pupil responses. Method: Twenty-five visually normal subjects, 18-30 years of age, participated in the experiment. They began by reading random words on a tablet computer for 20 minutes. Before and after the reading task, participants completed a symptom survey to assess DES severity. Subsequently, they were exposed to a blue background light of varying intensities within the dome of a pupilometer. The pupil light reflex was recorded for each intensity and analyzed. Results: The pupil diameter's EC50 value in response to blue light exhibited a statistically significant correlation with the total symptom score (p=0.0003), extrinsic symptom score (p=0.006) and intrinsic symptom score (p=0.0003). Similarly, the LogEC50 value also demonstrated a statistically significant correlation with total symptom score (p=0.002), extrinsic symptom score (p=0.02), and intrinsic symptom score (p=0.001). Conclusion: Subjects with greater DES scores exhibited reduced sensitivity when adapting to blue light, indicating a potential link between ipRGC function and DES symptoms. "
• 

  Upregulation of Gap Junction Connexins in Glaucoma

  Fareed, Nada (2024)

  Glaucoma is a leading cause of irreversible blindness, which is characterized by a progressive degeneration of the optic nerve and loss of retinal ganglion cells (RGCs). Glaucoma currently affects 3.5% of individuals aged 40 to 80 years, and the incidence of glaucoma is increasing together with life expectancies (Wagner et al., 2022). There is strong evidence that intercellular communication via gap junctions (GJs) facilitates secondary cell death, by means of the so-called “bystander effect” is which dying cells releases toxins that lead to the death of neighboring cells to which they are coupled (Akopian et al., 2014; 2017). Pharmacological blockade of GJs or genetic deletion of GJ subunit connexins Cx36 (Akopian et al., 2017) or Cx43 (Batsuuri et al., 2023) showed an increase in neuronal survivability by greater than 70% in glaucomatous retinas providing clear evidence that GJs can mediate secondary cell death, which can account for loss of most retinal neurons. Since Cx36 is expressed by GJs between retinal neurons and Cx43 is expressed between glial astrocytes, there are potentially two separate pathways that may underlie cell loss in glaucoma. This raises the important question of whether these pathways are independent mechanisms for cell death or are interdependent. Interestingly, both Cx36 and Cx43 are upregulated in glaucomatous retinas (Akopian et al., 2017; Batsuuri et al., 2023). Therefore, to assay the interdependence of bystander death mediated by Cx36- and Cx43-expressing GJs in glaucoma, we determined if their upregulation were interconnected. Understanding the potential interdependence of these two GJ-mediated bystander cell death pathways would help define potential targets for neuroprotection in glaucoma.
• Diurnal Variations in Scotopic and Photopic Flash Electroretinogram

  Wang, Jesse (2024)

  "Purpose: To determine the pattern of the diurnal variations in retinal responses measured with the full-field scotopic and photopic electroretinogram (ERG). Methods: Full-field flash ERGs were recorded with DTL electrodes after pupil dilation from 6 normal healthy subjects at 3AM, 9AM, 3PM and 9PM (one subject at 6AM, 12PM, 6PM, 12AM) on four separate days using a desktop ganzfeld ERG recording system (Diagnosys LLC). The test scotopic ERG test protocol consisted of 40 minutes of dark-adaptation followed by recordings with brief (<4ms) blue (440nm) test flashes in the range of 1x10-6 to 20 scot cd.s/m2. The photopic ERG test protocol consisted of 15 minutes of light-adaptation to 8 scot cd/m2 blue background followed recordings with brief red (690nm) test flashes in the range of 6x10-2 to 6.4 phot cd.s/m2 on the adapting background. The Scotopic Threshold Response (STR), scotopic and photopic b-waves and the Photopic Negative Response (PhNR) amplitudes were plotted as a function of test flash intensity and fit with the Naka-Rushton equation to extract the saturated amplitude (Vmax), slope (n) and semisaturation constant (K) parameters for each ERG measures. The fit parameters were plotted as a function of the time of the day when the recordings were performed to examine their diurnal variation. Saliva samples were collected and salivary melatonin was assayed (Salimetrics LLC) at 8 different time points during the day from each subject on one separate occasion and prior, during and after each ERG session. Results: The Vmax of the ERG measures demonstrated statistically significant systematic diurnal variation. The Vmax of the Scotopic b-wave and the STR did not change appreciably from 3AM to 9AM but thereafter gradually increased to reach a maximum value at 9PM. The difference in the mean value of the Vmax between the 3AM and 9PM recordings was statistically significant for the scotopic b-wave (173uv and 338uv, p=0.0013) and the STR (15uv and 22uv, p=0.03). with the halfway point for this amplitude increase being 11AM. The Vmax of the photopic b-wave and PhNR showed a steep increase from 3AM to 9AM and thereafter a more gradual increase at 3PM to slightly reduce again by 9PM. The difference in the mean value of the Vmax between the 3AM and 3PM recordings was statistically significant for the photopic b-wave (60uv and 92uv, p=0.04) and the PhNR (36uv and 61uv, p=0.019) with the halfway point for this amplitude increase being 6AM. Salivary metalonin concentration on average started to show an increase around 9AM from daytime baseline value of 1 pg/ml to a peak of 16 pg/ml around 3AM and then reduced to 4 pg/ml by 9AM. Conclusions: The maximal amplitude of the scotopic ERG parameters are achieved later during the day compared to the photopic ERG parameters that achieve maximal amplitudes at earlier times. The saturated amplitude of scotopic and photopic ERG measures have their lowest values around 3AM when salivary melatonin concentration is maximal. The relationship between the diurnal rhythms of melatonin and retinal function as measured by the ERG warrants further investigation. "
• Retinal Ganglion Cell Function in Diabetes Mellitus

  Vasiu, Sakshi (2024)

  "Purpose: To evaluate retinal ganglion cell function in diabetic patients with no retinopathy. Methods: The full-field photopic flash electroretinogram (ERG) was recorded from 11 diabetics patients (55.75 ± 14.77) and 11 age-matched controls (50.17 ± 15.18) with a ColorBurst TM handheld stimulator (Diagnosys LLC). The visual stimuli consisted of 40 ms duration red (640 nm) test stimuli of strengths ranging from 0.25 cd/m2 to 1500 cd/m2 delivered on and constant rod-saturating blue (470 nm) background of 7cd/m2. The Intensity response function of the PhNR and the b-wave amplitudes plotted as a function of stimulus strength were fitted with a generalized Naka-Rushton equation of the form V(I)/Vmax = In /(In +Kn ) and the fit parameters of K, n and Vmax were compared between the diabetic patients and control subjects. Visual field sensitivity was measured by behavioral perimetry using the Humphrey Visual Field Analyzer 10-2 and 24-2 SITA-standard tests. Structural parameters of the retina, namely area of the foveal avascular zone (FAZ), superficial vascular plexus density (SVD), deep vascular plexus density (DVD)and Retinal Nerve Fiber Layer (RNFL) thickness were measured with the Heidelberg OCTA. Linear regression analysis was used to study the correlation between affected ERG fit parameters and aspects of visual field sensitivity and retinal structural parameters. Results: The mean ages were not significantly different between the diabetic patients and control subjects. The average value of the PhNR semi-saturation constant for the diabetic patients and control subjects were 83.64+39.96 and 32.21+20 and the difference was statistically significant (p=0.0054). The average value of the PhNR slope for the diabetic patients and control subjects were 0.83+0.19 and 1.39+0.17 and the difference was statistically significant (p=0.0000018). PhNR Vmax was not statistically significantly different between the diabetic patients (30+7.12) and controls (30.18+6.45). The parameters of the Naka-Rushton fits to the b-wave responses were not significantly different between the two groups. A positive correlation was seen between the semi-saturation constant of the PhNR in diabetics and self-reported HbA1c% (r=0.72, m=22.8, p=0.029) and a negative correlation was observed between the semi-saturation constant of the PhNR and 10-2 mean sensitivity (r=0.67, m=-0.03, p=0.02). A positive correlation between the semi-saturation constant and SVD (r=0.66) and DVD (r=0.67) were seen in control subjects, whereas negative correlation was seen in diabetics eyes (r=0.5 and r=0.4). Conclusion: Retinal ganglion cell sensitivity is compromised in diabetic patients with no retinopathy as indicated by an increase in the value of the full-field PhNR semi-saturation constant while responses of their input neurons, namely bipolar cells, as reflected by the b-waves is relatively normal. Compromise of retinal ganglion cell function may underlie the earliest visual sensitivity changes diabetic patients. Further longitudinal studies are warranted to determine whether changes in ganglion cell function precedes changes in superficial and deep vessel density. "
• 

  Development of a Pediatric Digital Eye Strain Questionnaire

  Aguilar, Stephanie (2024)

  "Objectives: The aim of the present study was to create a valid and reliable method of determining to what extent children experience symptoms of digital eye strain (DES). Methods: The initial version of the pediatric digital eye strain questionnaire was developed using a literature review, consultation with experts and a pretest performed on 6-8-year-olds. A pilot test using a revised version of the questionnaire was performed on 70 6-12-year-old participants. Content validity was established by discussion with an expert. Construct validity was evaluated by performance of the pediatric DES questionnaire and the Computer Vision Syndrome Questionnaire (CVS-Q) by optometry students. Test-retest repeatability was tested using Bland Altman analysis and a significant cutoff score was established using the linear regression equation to determine the value equivalent to the previously assigned cutoff for the CVS-Q of 6. Results: The questionnaire evaluated 12 DES symptoms’ frequency in a simple, self-administrable method. The mean total score of the pilot test was 7. 45% of the participants in the pilot test had a significant score for DES. The questionnaire had excellent test-retest repeatability and construct validity r=0.81 (p<0.001). No significant correlation was found between the reported total number of hours of screen time per week and the total symptom score (r = 0.30, p = 0.47). Conclusions: This study indicates that almost half of children may be experiencing adverse ocular symptoms associated with screen use. The questionnaire provides a valid and reliable method for identification of DES symptoms in children ages 6-12 years. Optometrists, pediatricians and parents alike may find use for this questionnaire to evaluate for digital eye strain in children. "
• 

  The Role of Astroglial Connexin43 in Experimental Glaucoma.

  Batsuuri, Khulan (2023-08)

  Glaucoma is an irreversible blinding disease due to progressive loss of retinal ganglion cells (RGCs) and their axons. Astrocytes are glial cells that reside in the retinal nerve fiber layer (RNFL) closely to RGC bodies and unsheathe axons in the optic nerve head. Astrocytes play an important role in the pathogenesis of glaucoma. A unique feature of astrocytes is that they are extensively coupled by gap junctions (GJ) composed of connexin 43 (Cx43). In addition, unopposed Cx43 hemichannels can open in pathological conditions and release signaling molecules (e.g., ATP and excess glutamate). The role of astrocytic Cx43 GJ and hemichannels in glaucoma is unclear. Here we studied the effect of Cx43 deletion in astrocytes in normal conditions and in glaucomatous injuries. Results show that deletion of Cx43 does not affect normal retinal function, potentially due to direct coupling of astrocytes to Müller glia. Microbead-induced elevation of IOP increased Cx43 expression and GJ coupling in astrocytes. Importantly, astrocyte-specific deletion of Cx43 markedly reduced RGC death and preserved visual function in glaucomatous mice. Absence of Cx43 in astrocytes also reduced microglial activation in glaucoma but did not affect astrocyte reactivity. Additionally, intravitreal injections of Gap19 peptide, a selective Cx43 hemichannel blocker, markedly increased RGC survival and improved RGC function, indicating a contribution of activated Cx43 hemichannels in glaucoma progression. Therefore, targeting Cx43 hemichannels might be a new therapeutic approach to the treatment of glaucoma.

View more