THE NEUROTROPHIN RECEPTOR P75NTR AS A NEW PLAYER IN THE DEVELOPMENT OF CHOROIDAL NEOVASCULARIZATION

SUBIRADA, PV; VAGLIENTI, MV; JURADO AE; OBRIEN MP; LUNA JD; SARAGOVI, HU; ANASTASIA A; SANCHEZ, MC; BARCELONA, PF

Congreso; PAAO 2021 Annual Meeting; 2021

PAAO 2021 Annual Meeting

Propose: Choroidal neovascularization (CNV) is the pathological angiogenesis of the choroidal plexus and it represents a key feature in the wet form of age related macular degeneration (AMD). CNV is triggered by a pro-inflammatory response settled after a damage in the retinal pigmented epithelium (RPE). The growing neovessels invade the retina inducing photoreceptor degeneration. 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. Methods: C57BL/6 mice (2?4 months) were previously anesthetized and treated with four spots of argon green laser photocoagulation per eye. After 7 days of laser burn, we analyzed the NV on choroid?RPE flatmounts by isolectin IB4 staining using confocal microscopy. At the same time, using specific cell markers we characterize cells in the lesion area: CD105 (ECs), NG2 (pericytes), F4/80 (microglia), as wells as LRP1 cell distribution. In addition, protein levels of α2M and LRP1 were analyzed by WB and the inflammatory profile (IL1β, IL6, and TNFα) using qPCR assay. Finally, the retinal functionality was assessed by scotopic ERG. Results: Here, we aim to determine if p75NTR participates in the development of neuronal and vascular alterations in a mouse model of laser-induced CNV. Confocal images obtained 7 days after the laser injury showed overexpression of p75NTR in macrophages in the RPE-choroid, and in Muller glial cells around the lesioned area in the retina. When the laser treatment was provided to p75NTR KO mice, we observed a reduction in the area and perimeter of choroidal neovessels as well as a decreased macrophage infiltrate by immunostaining. In accordance, the neuronal dysfunction observed by electrorretinography (ERG) on this CNV model was reduced on p75NTR KO mice, as the amplitude of the a-wave was preserved after the laser. Conclusion: Our outcomes suggest that p75NTR would participate in the development of CNV.