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Sarah Walters, Christina Schwarz, Robin Sharma, William S. Fischer, David DiLoreto, Dasha Nelidova, Antonia Drinnenberg, Josephine Juettner, Botond Roska, David R. Williams, Jennifer J. Hunter, William H. Merigan; In vivo imaging of photoreceptor structure and function in a non-human primate model of retinal degeneration. Journal of Vision 2017;17(7):53. doi: 10.1167/17.7.53.
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Here we employ adaptive optics scanning light ophthalmoscopy (AOSLO) to assess cellular-scale changes in photoreceptor structure and function in a non-human primate model of retinal degeneration. The retinas of four macaques were subretinally injected with an adeno-associated viral construct designed to locally damage photoreceptors . Before and after injection, OCT and fundus SLO imaging was performed. Post-injection fundus SLO reflectance images revealed regions of decreased intensity, suggesting retinal damage. OCT of affected regions showed a reduction of intensity in outer retinal layers, primarily in the interdigitation zone. In two retinas, photoreceptors in both affected and unaffected regions were imaged with AOSLO in three modalities (λ=730nm): confocal reflectance, two-photon autofluorescence, and multi-offset detection. Confocal reflectance was used to capture directly backscattered light primarily originating from the inner/outer segment boundary and outer segment tip . Photoreceptors in affected regions exhibited reduced waveguiding, suggesting outer segment damage. In multi-offset detection, the confocal pinhole was displaced to capture multiply scattered light. Images from several aperture positions were combined to visualize inner segments , which were present in both affected and unaffected regions. Two-photon autofluorescence was used to excite all-trans-retinol and track its kinetics in response to light, which are indicative of retinoid production necessary for visual function and thus the functional state of the photoreceptors . In affected photoreceptors, there was no detectable increase in autofluorescence at light onset as was observed in unaffected photoreceptors. Therefore, photoreceptor assessment using AOSLO and OCT is consistent with inhibition of retinoid production due to outer segment damage while inner segments are preserved. This model of retinal degeneration shows promise for preclinical testing of vision restoration methods.
Meeting abstract presented at the 2016 OSA Fall Vision Meeting
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