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Glucocorticoid-Dependent Mechanisms in Photoreceptor Survival

  • Marisa A. Cubilla
  • Mauricio M. Castañeda
  • Tomás P. Bachor
  • Angela M. SuburoEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

Abstract

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 lx 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 studied by immunohistochemistry. Light exposure increased GRα immunoreactivity in photoreceptor nuclei and decreased RHO in nontreated mice. A greater decrease of RHO occurred in mice receiving MFP. DEX preserved RHO at levels found in nonexposed mice. DEX also protected RHO levels in exposed mice receiving MFP. Light exposure was accompanied by appearance of CC-3, which was completely blocked by DEX. MFP administration induced a greater increase of CC-3, but this 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.

Keywords

Glucocorticoids Glucocorticoid receptor Mifepristone Dexamethasone Light-induced retinal degeneration Rhodopsin Caspase-3 Cleaved caspase-3 Apoptosis 

Notes

Acknowledgments

MAC and MMC are research fellows from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. MAC was also a fellow of ANPCyT, MINCYT, during the initial phase of this project. AMS is Principal Researcher from CONICET. Studies reported here were funded by grants from Universidad Austral and ANPCyT (PICT 21399/2004 and PICTO 2008 0090). We are very grateful to Guillermo Gastón and Soledad Arregui for their skilful technical assistance.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Marisa A. Cubilla
    • 1
  • Mauricio M. Castañeda
    • 1
  • Tomás P. Bachor
    • 1
  • Angela M. Suburo
    • 1
    Email author
  1. 1.Facultad de Ciencias BiomédicasUniversidad AustralBuenos AiresArgentina

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