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2024
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SP_thesis_240906b_Sabina Poudel.pdf
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"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.
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