Abstract
Purpose :
Age-related macular degeneration (AMD) is a degenerative disease associated with ageing that affects both the pigment epithelium and the macula causing central vision loss. This disease is characterized by choroidal neovascularization (CNV), which causes retinal edema and subsequent damage to the photoreceptor cells. Currently, treatments directed against vascular endothelial growth factor (anti-VEGF) slow the progression of blindness in wet AMD. In recent years, the laser-induced CNV model is a gold standard animal model and has played an essential role in the development of anti-VEGF and/or PDGF-based therapies for wet AMD.
Methods :
In this study, we optimized and characterized an animal model, using the Zeiss Visulas Green clinical laser in pigmented rats, forming choroidal and retinal lesions at different intensities to determine which most accurately mimics the process of CNV. To assess vessel formation (neovascularization) and lesion progression, in vivo Optical Coherence Tomography (OCT) and Fundus Fluorescein Angiography (FFA) were performed during 21 days. In addition, postmortem characterization studies were performed by RNA and immunohistochemistry (IHC) analysis to study different biomarkers involved in the neovascular process. Finally, statistical analysis was run using GraphPad Prism 6.0.
Results :
The results obtained confirm that the application of different laser intensities have different and significant effects on the induction and maintenance of the ocular lesion, the percentage of neovascularization, the biomarker profile, and the degree of tissue inflammation. The description of such changes may help to understand the earliest stages of wet-AMD and other angiogenic-related retinal pathologies, establishing a new preclinical model that may lead to the discovery of the underlying pathophysiological processes related to novel therapeutic targets other than VEGF and PDGF.
Conclusions :
This work provides evidence that new preclinical model may help to understand the earliest stages of wet-AMD and other angiogenic-related retinal pathologies and may lead to the discovery of the underlying pathophysiological processes related to novel therapeutic targets other than VEGF and PDGF.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.