June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Evaluation of the Fibrotic Change Associated with Laser Induced Choroidal Neovascularization in the Nonhuman Primate
Author Affiliations & Notes
  • Flavia Leao Barbosa
    Virscio Inc, Connecticut, United States
    St. Kitts Biomedical Research Foundation, Saint Kitts and Nevis
  • Merissa O'Connor
    Virscio Inc, Connecticut, United States
    St. Kitts Biomedical Research Foundation, Saint Kitts and Nevis
  • Richard Bouffard
    Virscio Inc, Connecticut, United States
    St. Kitts Biomedical Research Foundation, Saint Kitts and Nevis
  • Jennifer Cann
    Virscio Inc, Connecticut, United States
    St. Kitts Biomedical Research Foundation, Saint Kitts and Nevis
  • Matthew Lawrence
    Virscio Inc, Connecticut, United States
    St. Kitts Biomedical Research Foundation, Saint Kitts and Nevis
  • Footnotes
    Commercial Relationships   Flavia Leao Barbosa None; Merissa O'Connor None; Richard Bouffard None; Jennifer Cann None; Matthew Lawrence None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2175. doi:
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      Flavia Leao Barbosa, Merissa O'Connor, Richard Bouffard, Jennifer Cann, Matthew Lawrence; Evaluation of the Fibrotic Change Associated with Laser Induced Choroidal Neovascularization in the Nonhuman Primate. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2175.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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