INDUCTION OF STRESS GRANULES IN GANGLION CELLS AND THE INNER NUCLEAR LAYER IN A MODEL OF RETINAL DEGENERATION CAUSED BY CONSTANT LED LOW-INTENSITY LIGHT.

PENAZZI LG; BENEDETTO MM; MALCOLM M; BRUERA M; GUIDO ME; CONTÍN MA; GARBARINO PICO E

Mendoza

Congreso; LVIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; 2022

SAIB

The retina is a specialized light perception tissue that has evolvedin an environment in which light intensity values vary daily byseveral orders of magnitude as a consequence of the day/night cycle.During the day the retina is prepared to deal with the deleteriouseffects of light, but during the night, these protective mechanismsare diminished. Artificial light and the use of devices with luminousLED screens -such as cell phones, monitors or TVs- expose our retinasto light at times when the phototoxic effect cannot be avoided. Inour laboratory we have developed a model of retinal degenerationcaused by constant low intensity LED light in rats, in whichaccumulation of reactive oxygen species (ROS) and progressive celldeath of cones and rods is observed. In the present work, consideringthat cellular stress induces the formation of stress granules (SGs),and that they have a protective role, we analyzed the presence ofthese ribonucleoprotein biocondensates in rat retinas maintainedunder constant light. SGs are formed in the cytoplasm as part of theintegrated stress response, in which global protein synthesis isinhibited so that translation initiation complexes accumulate andgive rise to liquid-liquid phase transitions giving origin to thesebiocondensates. Since they had not been described in this tissue, wefirst characterized them by immunohistochemistry (IHC) using twodifferent antibodies (against eIF3 and G3BP1 markers) and byFluorescence in situ hybridization (FISH), in control retinas andretinas treated with hydrogen peroxide or sodium arsenite (oxidativestress). We also did it on primary cultures of total retina. Once wewere certain that we were detecting SGs, we proceeded to quantifythem by IHC in the different retinal layers in control animals (keptunder a 12 h light-12 h dark cycle, LD) and rats kept under constantLED light (LL) for 2-8 days (model of retinal degeneration). We foundthat retinas subjected to LL presented a significantly larger numberof SGs. Notably, ganglion cells presented the highest number of SGs,cells of the inner nuclear layer also presented several granules,while the photoreceptor layer (cones and rods) presented almost noSGs. That is to say that the neurons that manage to survive duringthe first 8 days of LL are the ones that form more SGs, coincidingwith the protective role attributed to them. This correlation hasallowed us to propose the hypothesis that SGs would favor neuronalsurvival in the context of retinal photodamage.p { line-height: 115%; margin-bottom: 0.25cm; background: transparent }a:link { color: #000080; so-language: zxx; text-decoration: underline }