Glucocorticoid and progesterone mechanisms in photoreceptor survival

CUBILLA M. A; MARQUIONI RAMELLA MD; BERMÚDEZ V; TATE PS; MARAZITA MC; SUBURO AM

EXPERIMENTAL EYE RESEARCH

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2019

0014-4835

Death of retinal photoreceptors is the basis of prevalent blinding diseases. Since dexamethasone and progesterone are known as photoreceptor neuroprotectants we studied their effects in two retinal degeneration models in male mice: the selective photoreceptor deaths induced by mifepristone or light exposure. Our goals were: to compare effective doses and to evaluate their interactions with pro and antiapoptotic molecules, glucocorticoid receptors α and β (GRα and GRβ), and rhodopsin.Only photoreceptors were affected in both models, but light exposed retinas showed the dorsotemporal localization of damaged photoreceptors. However, dexamethasone and progesterone were equally beneficial for their survival, preserving more than 95% photoreceptor nuclei in each model. Assessment of cell death regulators showed that both steroids could activate cell survival promoting molecules in healthy retinas, with BCL-XL displaying the most remarkable changes. Significant modifications of cell death regulators appeared when retinas exposed to injury were treated with dexamethasone or progesterone. Changes of GRα in both degeneration models were consistent with a mechanism of ligand-induced downregulation of receptor expression. In addition, GRβ might be upregulated by progesterone. Importantly, we have also found that both dexamethasone and progesterone increased retinal rhodopsin stores