The role of glucocorticoids in photoreceptor survival

SUBURO, AM; CUBILLA, MA; CASTAÑEDA, M; LUZZANI, G; BACHOR, T.

Mont Tremblant, Quebec

Simposio; XIV International Symposium on Retinal Degeneration RD2010; 2010

ORGANIZING COMMITTEE: Matthew M. LaVail, Ph.D., Joe G. Hollyfield, Ph.D., Robert E. Anderson, M.D., Ph.D., John Ash, Ph.D., Christian Grimm, Ph.D.

Glucocorticoids are known to improve photoreceptor survival in animal models of light-induced retinal degeneration, laser photocoagulation and subretinal hemorrhage. However, little is known about the role of these steroids in the normal retina. Therefore, we studied the effect of a single dose of mifepristone (MFP), an antagonist of the glucocorticoid receptor (GR), on the retina of Balb-c mice bred and cared bred under standard illumination conditions (12:12 h light: dark; less than 60 lux). Mice received saline, MFP, dexamethasone (DEX) or MFP + DEX injections at noon and were euthanatized 6 hours later. Cleaved-caspase 3 (CC3), Bcl-XL and Bcl-2 were assayed by Western blot. Retinal extracts from normal rats contained Bcl-XL but no CC3 or Bcl-2. After MFP injection, the Bcl-XL band became undetectable whereas CC3 and Bcl-2 bands were consistently found. The MFP pattern could be partially or completely reversed according to DEX dose. No changes in the control pattern were detected after DEX alone. After MFP treatment, hyperchromatic cell nuclei appeared in the outer nuclear layer. Our findings show that MFP induced apoptosis in the photoreceptor layer, implying that endogenous glucocorticoids would be essential for photoreceptor survival.