Stereoid receptors and photorreceptor survival

MARQUIONI-RAMELLA, MD.; SUBURO, AM.; TATE, P.; MARAZITA, MC.

Mar del Plata

Congreso; LXIII Reunión Científica Anual de la SAIC; 2018

Photoreceptors survival is affected in various retinal diseases. Steroid hormones and glucocorticoids (GC) can be neuroprotective and it has been suggested that progesterone (PROG) and dexamethasone (DEX) may be beneficial. So the objective is to investigate the mechanisms of neuroprotection involved by PRG and DEX, in two models of mouse photoreceptor degeneration: phototoxic degeneration and degeneration induced by mifepristone (MFP). As well as the location of the GCs and PROG receptors. We use male balb/c mice (5-7 weeks) reared under cyclic illumination (≤ 60 lux). To generate damage, animals were exposed 48hs to 1500lux or received an injection of MFP (10mg/Kg), with or without steroid treatment (DEX 4mg/Kg/day, PROG 1 or 4 mg/Kg/day) for two days. In both models, the control groups received saline solution. Animals were sacrificed at day 2. The immunofluorescence revealed the presence of GR and PROG receptors in the retina, data corroborated by WB of the whole retinaand also form isolated rod outer segments (ROS). WBs demonstrated the presence of cleaved caspase 3 (CC-3) in both degeneration models, but not in those treated with PROG 4mg/Kg. The apoptotic regulator Bcl-2 showed an increase in injured retinas, while Bcl-XL disappeared in both degeneration models. p-H2AX increases considerably under both damage, but steroids treatment reduced its expression considerably. We found that only the CNE have TUNEL+ nuclei, that was higher in animals exposed to light than in those treated with MFP, in both cases PROG and DEX reduced the number of positive nuclei. The same was seen with CC-3 immunohistochemistry. We conclude that both PROG and DEX are neuroprotectors because they prevented photoreceptors death in both models of degeneration, demonstrated by the absence of CC-3 and alterations in the levels of Bcl-2, Bcl-XL and p-H2AX, as well as by reducing TUNEL+ nuclei.