The neurotrophin receptor p75NTR as a new player in the development of choroidal neovascularization

SUBIRADA, PAULA V.; VAGLIENTI, MARIA V.; OBRIEN, MP; JURADO, AE; LUNA PINTO, JD; HORACIO URI SARAGOVI; SÁNCHEZ, MARÍA C.; ANASTASIA, A.; BARCELONA, PABLO F.

Congreso; Annual Meeting of The Association for Research in Vision and Ophthalmology ? ARVO; 2021

ARVO

Purpose : Choroidal neovascularization (CNV) is a key feature in the wet form of age related macular degeneration (AMD). Current treatments are inefficient, therefore a better understanding of the pathophysiology of AMD is necessary to develop novel therapeutic approaches. The p75 neurotrophin receptor (p75NTR) is recognized as one of the main surface proteins involved in the transduction of death signals and recently also vascular changes. Here, we aim to determine if p75NTR participates in the development of neuronal and vascular alterations in a mouse model of laser-induced CNV.Methods : Briefly, mice were anesthetized and their pupils were dilated, then 4 injuries were performed in the retina using a photocoagulation laser with a 532nm wavelength slit lamp. 7 days after laser mice were subjected to electrorretinography (ERG) studies, and posterior sacrifice. Retinas and RPE-Choroid were processed separately for Western blot and immunofluorescence assays in whole mounts and criosections. Colocalization was analysed in tissues double labeled with p75NTR and one of the following cell markers: F4/80 (macrophages), NG-2 (pericytes), Isolectin IB-4 (blood vessels), glial fibrillary acid protein (glial cells) or β-actin (neurons). WT (N=17) and p75NTR KO (N=12) mice were included in the experimental design and animals without CNV were used as control. GraphPad Prism program was employed for statistical analysis and one way ANOVA or t-test analysis was performed accordingly.Results : In WT rodents, Western blot of neural retinas of CNV mice exhibited an increased expression of p75NTR protein levels respect to control (p<0,05). Confocal images showed overexpression of p75NTR in macrophages in the RPE-Choroid, and in Muller glial cells around the injured area in the retina. These alterations in the CNV model were accompanied with neuronal dysfunction observed as a reduction in the amplitude of the a-wave by ERG, which was preserved in p75NTR KO mice. In accordance, p75NTR KO mice showed a reduction in the area and perimeter of choroidal neovessels (p<0,05) as well as a decreased macrophage infiltrate by immunostaining.Conclusions : Altogether these preliminary findings suggest that p75NTR would participate in the development of CNV.