Morgan, J. I. W. | bioRxiv Science

bioRxiv2021

Short-term assessment of subfoveal injection of AAV2-hCHM gene augmentation in choroideremia using adaptive optics ophthalmoscopy

Subretinal injection for gene augmentation in retinal degenerations forcefully detaches the neural retina from the retinal pigment epithelium (RPE), potentially damaging photoreceptors and/or RPE cells. Here, we use adaptive optics scanning light ophthalmoscopy (AOSLO) to assess the short-term integrity of the cone mosaic following subretinal injections of AAV2-hCHM gene augmentation in subjects with choroideremia (CHM). Nine adult CHM patients received uniocular subfoveal injections of low dose (5x1010 vector genome (vg) per eye, n=5) or high dose (1x1011 vg per eye, n=4) AAV2-hCHM. The macular regions of both eyes were imaged pre- and one-month post-injection using a custom-built, multimodal AOSLO. Post-injection cone inner segment mosaics were compared to pre-injection mosaics at multiple regions of interest (ROIs). Post-injection AOSLO images showed preservation of the cone mosaic in all 9 AAV2-hCHM injected eyes. Mosaics appeared intact and contiguous one-month post-injection, with the exception of foveal disruption in one patient. Co-localized optical coherence tomography showed foveal cone outer segment (COS) shortening post-injection (significant, n=4; non-significant, n=4; unchanged, n=1). Integrity of the cone mosaic is maintained following subretinal delivery of AAV2-hCHM, providing strong evidence in support of the safety of the injections. Minor foveal thinning observed following surgery corresponds with short-term COS shortening rather than cone cell loss.

neuroscience↗

bioRxiv2018

Spatial summation in the human fovea: the effect of optical aberrations and fixational eye movements

Psychophysical inferences about the neural mechanisms supporting spatial vision can be undermined by uncertainties introduced by optical aberrations and fixational eye movements, particularly in fovea where the neuronal grain of the visual system is fine. We examined the effect of these pre-neural factors on photopic spatial summation in the human fovea using a custom adaptive optics scanning light ophthalmoscope that provided control over optical aberrations and retinal stimulus motion. Consistent with previous results, Riccos area of complete summation encompassed multiple photoreceptors when measured with ordinary amounts of ocular aberrations and retinal stimulus motion. When both factors were minimized experimentally, summation areas were essentially unchanged, suggesting that foveal spatial summation is limited by post-receptoral neural pooling. We compared our behavioral data to predictions generated with a physiologically-inspired front-end model of the visual system, and were able to capture the shape of the summation curves obtained with and without pre-retinal factors using a single post-receptoral summing filter of fixed spatial extent. Given our data and modeling, neurons in the magnocellular visual pathway, such as parasol ganglion cells, provide a candidate neural correlate of Riccos area in the central fovea.

neuroscience↗