MIFEPRISTONE REDUCES PHOTORECEPTOR SURVIVAL IN LIGHT-EXPOSED RETINAS

CUBILLA MA; CASTAÑEDA MM; BACHOR TP; SUBURO A.M

ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY.

SPRINGER-VERLAG BERLIN

Año: 2011

0065-2598

Glucocorticoids increase photoreceptor survival in rodent models of acquired and genetic retinal degeneration, but little is known about mechanisms underlying retinal protection. Therefore, we exposed male Balb-c mice to 1,500 lux during 2 or 4 days and compared photoreceptor damage after administration of dexamethasone (DEX) or mifepristone (MFP), a blocker of glucocorticoid receptors (GRs). To evaluate the course of light-induced retinal degeneration we measured levels of rhodopsin (RHO) and cleaved caspase-3 (CC-3) using semiquantitative Western blots. The α variant of GR (GRα) and CC-3 were also evaluated by immunohistochemistry. Light exposure increased GRα immunoreactivity in photoreceptor nuclei and decreased RHO in non-treated mice. RHO was much lower in the presence of MFP, but remained stable under DEX, even in the presence of MFP (MFP+DEX). Light exposure was accompanied by appearance of CC-3, which was completely blocked by DEX. MFP administration induced a greater increase of CC-3, which was only partially reversed by DEX. Preservation of RHO and decrease of caspase-3 activation would be involved in DEX protection of light-induced retinal injury. Photoreceptor damage was aggravated by MFP; however, effects of DEX on CC-3 changes induced by exposure and MFP suggest that cell death mechanisms can still be active in spite of RHO preservation.