Abstract
Purpose :
Nonhuman primate (NHP) laser-induced choroidal neovascularization (CNV) has been a valuable test system for the evaluation of anti-neovascular interventions, accurately predicting the comparative clinical efficacy of candidates to standard of care of anti-VEGF therapeutics for wet age-related macular degeneration (AMD). The utility of NHP CNV modeling in predicting the effect of candidate therapeutics to ameliorating the fibrotic component of wet AMD-associated pathophysiology has not been established. The aim of the current study was to evaluate the extent and time course of fibrosis associated with CNV complex formation induced by laser photocoagulation in the African green monkey
Methods :
Following baseline tonometry, slit lamp biomicroscopy, fundoscopy, color fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT), four monkeys underwent laser disruption of Bruch’s membrane by placement of six laser spots symmetrically within the perimacular region in each eye by an ophthalmologist employing an Iridex Oculight TX 532 nm laser with a laser duration of 100 ms, spot size 50 µm, power 750 mW. Animals were euthanized at Day 9 and Day 28 following repeat FA and OCT imaging. Eye globes were enucleated and processed. Hematoxylin and eosin (H&E) histology and fibrosis staining with collagen hybridizing peptide (CHP) and Masson’s Trichrome were performed and analyzed semi-quantitatively by a pathologist and quantitatively using Visiopharm image analysis software
Results :
Histopathologic assessment of CNV complex boundary and extent correlated to CNV complex definition by in-life OCT imaging and measurement, and FA lesion intensity and scoring. The extent of fibrosis as determined by CHP IHC and Masson’s Trichrome staining also correlated with lesion severity assessed by H&E and in-life imaging endpoints and exhibited temporal differences in proportionate extent at 9 and 28 days
Conclusions :
These data confirm fibrotic processes to be a component of the pathophysiology of CNV in the green monkey following laser disruption of Bruch’s membrane, and the capacity to quantitatively assess by CHP staining of collagen deposition. Addition of fibrosis analysis to the NHP CNV model will permit quantitative evaluation of the tissue pharmacodynamic effect of anti-fibrotic or dual mechanism therapeuti
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.