Autophagy participation in a mouse model of Oxygen-Induced Retinopathy (OIR).

SUBIRADA P; RIDANO ME; PAZ MC; BONACCI G; FADER KAISER C; SANCHEZ MC

Mar del Plata, Buenos Aires

Congreso; LI Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2015

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Autophagy has been implicated in neurodevelopment and other physiological processes. However, it has also been involved in cell survival or death in some diseases. In retinopathy of prematurity (ROP), the hypoxic insult generates damage in organelles and misfolding of proteins, which could be eliminated by autophagy. Herein, we analyze the role of autophagy in the OIR model, which closely resemble ROP and Diabetic Retinopathy. C57/BL6 mice exposed to 75% O2 from postnatal day (P) 7 to 12 were brought to room air (RA) for additional 9 days (P26). Age-matchedmice maintained in RA for 26 days, respectively, were used as control. All mice were injected intraocularly with 3-methyladenine (an autophagy inhibitor) or saline, into one eye of each mouse, at two different times: P12 and P17. Animals were sacrificed at P26. Retinal function and morphology, cell death (TUNEL) and immunofluorescence staining for autophagy (LC3) showed that the injection at P12, resulted in the more profound damage in both conditions, even though structural and functional alterations were more severe in OIR mice. Western blot of retinas allowed us to corroborate changes in stress and detoxifying proteins. In OIR, LC3 staining was observed in GFAP positive cells coinciding with results obtained in Müller cells under hypoxic conditions. The results suggest that autophagy blockade is detrimental for retinal tissue.