June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
The neurotrophin receptor p75NTR as a new player in the development of choroidal neovascularization
Author Affiliations & Notes
  • Paula Virginia Subirada Caldarone
    Instituto de Investigacion Medica Mercedes y Martin Ferreyra, Cordoba, Córdoba, Argentina
    Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Cordoba, Córdoba, Argentina
  • Maria Victoria Vaglienti
    Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Cordoba, Córdoba, Argentina
  • Maria Paula O`brien
    Romagosa Private Eye Center. VER foundation, Cordoba, Córdoba, Argentina
  • Alejandra Jurado
    Romagosa Private Eye Center. VER foundation, Cordoba, Córdoba, Argentina
  • Jose D Luna Pinto
    Romagosa Private Eye Center. VER foundation, Cordoba, Córdoba, Argentina
  • Horacio Uri Saragovi
    Lady Davis Institute for Medical Research, Montreal, Quebec, Canada
  • Maria Cecilia Sanchez
    Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Cordoba, Córdoba, Argentina
  • Agustín Anastasía
    Instituto de Investigacion Medica Mercedes y Martin Ferreyra, Cordoba, Córdoba, Argentina
  • Pablo Federico Barcelona
    Centro de Investigaciones en Bioquimica Clinica e Inmunologia, Cordoba, Córdoba, Argentina
  • Footnotes
    Commercial Relationships   Paula Subirada Caldarone, None; Maria Vaglienti, None; Maria O`brien, None; Alejandra Jurado, None; Jose Luna Pinto, None; Horacio Saragovi, None; Maria Sanchez, None; Agustín Anastasía, None; Pablo Barcelona, None
  • Footnotes
    Support  SECYT UNC (411-2018 and 068-2020); FONCYT-PICT 2016 (0696); ISN-CAEN 2016.
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 643. doi:
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      Paula Virginia Subirada Caldarone, Maria Victoria Vaglienti, Maria Paula O`brien, Alejandra Jurado, Jose D Luna Pinto, Horacio Uri Saragovi, Maria Cecilia Sanchez, Agustín Anastasía, Pablo Federico Barcelona; The neurotrophin receptor p75NTR as a new player in the development of choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2021;62(8):643.

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

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Abstract

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.

This is a 2021 ARVO Annual Meeting abstract.

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