RETINAL DEGENERATION PROMOTED BY EX- CESS OF LIGHT: MECHANISM OF CELL DEATH AND NEUROINFLAMMATORY RESPONSE

BRUERA M; BENEDETTO M; DEGANO, A. L.; CONTIN MA

Mar del PLata

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)

The overexposure to artificial lights may be one of the many factorsthat can induce the interruption of retinal homeostasis, promotingthe injury of this tissue by photoreceptor cell (PhC) death that resultsin retinal degeneration (RD). Previously, we have establishedan animal model of light-induced RD in Wistar rats through constantexposure to LED light (200 lux). Using this model, we demonstratedthat, after 5 days of exposure, the retina suffers important functionaland structural changes including PhC death, opsins re-localizationand increased oxidative stress. In order to elucidate the differentmolecular mechanisms leading to RD promoted by light excess, theaim of this work was to study the glial and inflammatory responseand cell death proteins expression in animals exposed from 2 to8 days of constant LED light. Retinas were processed either forWB, Q-PCR or IHC; and evaluated the expression of glial markers(GFAP and Iba1), inflammatory cytokines (TNFα, IL-6, CX3CR1,CCL2) and proteins involved in death cell processes (BAX, BCL-2,CASP8, TNFR1, RIPK3 and TLR4). After 6 days of exposure (LL6),we observed a significant increase in GFAP expression (p<0.001),the total number of iba1+ microglial cells (p<0.01) and the number ofthese activated cells (amoeboid shaped) in the PhC layer (p<0.01)compared to control animals. At the same time-point, we observedincreases in TNFα and IL-6 (p<0.05), CX3CR1 (p<0.01) and CCL2(p<0.001) mRNA expression. These results suggest that constantexposure to LED light promotes glial activation indicating a neuroinflammatoryresponse to light damage. On the other hand, there wereno changes in the mRNA expression of pro-apoptotic proteins BAXand CASP8 at the times studied, but were changes in the anti-apoptoticprotein BCL-2 (LL2, p<0.05), necroptosis protein RIPK3 (LL6,p<0.01) and receptors TNFR1 and TLR4 (LL2, p<0.05) respect tocontrols animals; indicating that necroptosis may be the principalmechanism of PhC death