Up-regulation of pro-angiogenic pathways and induction of neovascularization by an acute retinal light damage

A Tisi,G Parete,V Flati,R Maccarone

doi:10.1038/s41598-020-63449-y

Abstract

The light damage (LD) model was mainly used to study some of the main aspects of age related macular degeneration (AMD), such as oxidative stress and photoreceptor death. Several protocols of light-induced retinal degeneration exist. Acute light damage is characterized by a brief exposure (24 hours) to high intensity light (1000 lux) and leads to focal degeneration of the retina which progresses over time. To date there are not experimental data that relate this model to neovascular events. Therefore, the purpose of this study was to characterize the retina after an acute light damage to assess whether the vascularization was affected. Functional, molecular and morphological investigations were carried out. The electroretinographic response was assessed at all recovery times (7, 60, 120 days after LD). Starting from 7 days after light damage there was a significant decrease in the functional response, which remained low up to 120 days of recovery. At 7 days after light exposure, neo-vessels invaded the photoreceptor layer and retinal neovascularization occurred. Remarkably, neoangiogenesis was associated to the up-regulation of VEGF, bFGF and their respective receptors (VEGFR2 and FGFR1) with the progression of degeneration. These important results indicate that a brief exposure to bright light induces the up-regulation of pro-angiogenic pathways with subsequent neovascularization.

Highlights

The light damage (LD) model was mainly used to study some of the main aspects of age related macular degeneration (AMD), such as oxidative stress and photoreceptor death
We demonstrated for the first time that acute light damage leads to the modulation of the most relevant pathways involved in neovascular AMD” (nAMD), in particular the vascular endothelial growth factor (VEGF) pathway, which is a fundamental feature in nAMD
Acute light damage (LD) is a model of retinal degeneration used worldwide to study some of the main features of AMD

Summary

Introduction

The light damage (LD) model was mainly used to study some of the main aspects of age related macular degeneration (AMD), such as oxidative stress and photoreceptor death. We demonstrated for the first time that acute light damage leads to the modulation of the most relevant pathways involved in nAMD, in particular the VEGF pathway, which is a fundamental feature in nAMD. This was associated with neovascularization, retinal degeneration and impairment of retinal function. We demonstrated for the first time that acute light damage leads to the modulation of the most relevant pathways involved in nAMD, in particular the VEGF pathway

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