Retinal degeneration promoted by excess of light: mechanism of cell death and neuroinflammatory response

BRUERA, MANUEL G.; MARIA M BENEDETTO; ALICIA L. DEGANO; CONTIN, MARÍA A

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias ? LXVII Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC) 2022; 2022

The overexposure to artificial lights may be one of the many factors that can induce the interruption of retinal homeostasis, promoting the injury of this tissue by photoreceptor cell (PhC) death that results in retinal degeneration (RD). Previously, we have established an animal model of light-induced RD in Wistar rats through constant exposure to LED light (200 lux). Using this model, we demonstrated that, after 5 days of exposure, the retina suffers important functional and structural changes including PhC death, opsins re-localization and increased oxidative stress.In order to elucidate the different molecular mechanisms leading to RD promoted by light excess, the aim of this work was to study the glial and inflammatory response and cell death proteins expression in animals exposed from 2 to 8 days of constant LED light. Retinas were processed either for WB, 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 of these activated cells (amoeboid shaped) in the PhC layer (p<0.01) compared to control animals. At the same time-point, we observed increases in TNFα and IL-6 (p<0.05), CX3CR1 (p<0.01) and CCL2 (p<0.001) mRNA expression. These results suggest that constant exposure to LED light promotes glial activation indicating a neuroinflammatory response to light damage.On the other hand, there were no changes in the mRNA expression of pro-apoptotic proteins BAX and CASP8 at the times studied, but were changes in the anti-apoptotic protein BCL-2 (LL2, p<0.05), necroptosis protein RIPK3 (LL6, p<0.01) and receptors TNFR1 and TLR4 (LL2, p<0.05) respect to controls animals; indicating that necroptosis may be the principal mechanism of PhC death.