Studies about the cooperative signaling between p75NTR and Trk receptors in the modulation of choroidal angiogenesis

PAULA VIRGINIA SUBIRADA; ALBANA TOVO; MARIA VICTORIA VAGLIENTI; LUNA, JOSÉ D.; SÁNCHEZ, MC; AGUSTÍN ANASTASIA; BARCELONA, PABLO F.

Virtual

Congreso; XXXVI Congreso Anual de Sociedad Argentina de Investigación en Neurociencias; 2021

SAN

The p75 neurotrophin receptor (p75NTR) is a transmembrane protein that mediates neuronal growth, survival and death. p75NTR can couple to different co-receptors to transduce intracellular signals. New evidences point p75NTR as a key player in the development of vasculopathies. Our results show that p75NTR increases 7 days post laser in retinal glia and RPE (retinal pigment epithelium)-choroid infiltrate (f4/80+) of mice with choroidal neovascularization (CNV). The deletion of the receptor reduced CNV and prevented photoreceptor dysfunction. It has been reported that p75NTR can potentiate Trk signalling in some scenarios. Thus, we aim to determine if p75NTR modulates Trk activation to modify neovessel formation in a mouse model of laserinduced CNV. In order to estimate Trk activation, we performed western blot assays to detect the activation ofone of its downstream pathways: MAPK/ERK. We detected decreased expression of phosphor-ERK in CNV mice respect to control, both in retina and in RPE-choroid 7 days post laser. Immunostaining did not show localization of pan-Trk nor p-ERK in retinal glia identified by GS and GFAP respectively. Similarly, no overlapping was observed between pan-Trk and RPE-Choroid infiltrate. Surprisingly, p75NTRKO mice showed increased expression of p-ERK 7 days after laser in retina and RPE-Choroid. In sum, our results suggest that the formation of vascular tufts in CNV is not mediated by the cooperative signalling between p75NTR and Trk receptors.