Abstract
Purpose :
Geographic atrophy (GA) is a retinal feature of advanced nonexudative age-related macular degeneration, characterized by the degeneration of retinal pigment epithelium (RPE) and photoreceptor cells. Non-human primate (NHP) models are ideal due to their anatomical and genetic similarities shared with humans. However, developing retinal degeneration in NHP to recapitulate the disease phenotype is still challenging. This study aims to establish a laser-induced NHP retinal degeneration model and characterize the morphological features of atrophy lesions.
Methods :
6 male cynomolgus monkeys aged 6-8 years were included. Retinas were lasered at superior and inferior macular regions using a 532 nm laser unilaterally, with different powers (130, 150, and 250 mW) at 50 μm spot size, and each lasered area consisting of 32 laser buns in a confluent pattern. The fundus photographs (FP), fundus fluorescein angiograms (FFA), autofluorescence (AF), optical coherence tomography (OCT), and OCT angiography (OCTA) exams were performed every month for up to 4.5 months.
Results :
One month after laser, pigment changes can be observed in the lasered area by FP with hypo and hyperpigmentation, which corresponded to window defect and fluorescence blockage in FFA. Other features of FFA include hypofluorescence due to hypoperfusion, and focal hyperfluorescence due to choroidal neovascularization. Decreased AF in the lasered region can be observed in all laser settings, with increased AF at the borders of atrophy in different phenotypes. Right after laser induction, retinal edema with increased retinal thickness was observed by OCT in the modeling area at all laser settings. Outer retinal thinning can be observed at 1 month after laser, and subsequently stable to 4.5 months, with a relatively preserved inner retina. Other OCT features include ablation of the outer nuclear layer, elevation/thickening of RPE, and migration of hyperreflective dots in the retina. Choriocapillaris loss can be observed by OCTA in the corresponding atrophy area. Higher-power lasers have a higher chance of causing retinal abnormalities than lower-power, including retinal detachment, subretinal hemorrhage, incomplete RPE, and more severe fluorescent leakage.
Conclusions :
A laser induced retinal atrophy NHP model was established, which mimics the morphological features of advanced GA and provides a valuable platform for preclinical evaluation of new therapies for retinal degeneration.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.