Progesterone Protects Photoreceptors From Light-induced Damage.

CUBILLA, MA; BACHOR, TP; BERMUDEZ, V; MARQUIONI, MD; SUBURO, AM

Fort Lauderdale

Congreso; Association for Research in Vision and Ophthalmology (ARVO) 2012 Annual Meeting; 2012

Association for Research in Vision and Ophthalmology

Purpose:We have previously shown that mifepristone (MFP), a blocker of progesterone (PRG) and glucocorticoid (GC) receptors (GRs), increases retinal light-induced damage. Although phototoxic lesions can be prevented by dexamethasone (DEX), a pure GR agonist, PRG receptors could also be involved. Therefore, we tested the effect of this steroid on light-exposed retinas. Methods:Experimental work was done according to the ARVO Statement for the use of animals. Male Balb-c mice (35-45 days-old), bred under standard illumination conditions (12:12 h light: dark; < 60 lux), remained in complete darkness for 24 h. Control mice returned to standard illumination, whereas experimental animals were exposed to 1,500 lux. These mice received progesterone (1 mg/kg/day) or its vehicle. The following parameters were evaluated at 2-4 days of exposure: preservation of the outer nuclear layer (ONL) in neutral red-stained cryosections; DNA fragmentation in the ONL by TUNEL; and rhodopsin (RHO) and cleaved caspase-3 (CC-3) by Western blot. Results:After 2 days of light exposure, the ONL showed numerous TUNEL+ nuclei, and retinal extracts showed a reduction of RHO levels and the appearance of CC-3 protein. In exposed animals receiving PRG, the ONL had no TUNEL+ nuclei, and extracts did not contain CC-3 protein. RHO was equal or higher than in controls. No structural damage could be discerned after 2 day exposure, therefore, we used 4-day exposed retinas to evaluate changes in the number of rows in the ONL. In animals receiving VHC injections, photoreceptor nuclei were missing in about 50% of the retinal area. Largest damage appeared in the dorsotemporal quadrant, close to the optic nerve head. No abnormalities of ONL could be detected in PRG-treated mice Conclusions:Progesterone prevented light-induced damage in mice retina exposed to 1,500 lux. The PRG (1 mg/kg) protective effect was equal or better than the protection provided by DEX (4 mg/kg, Cubilla et al., in preparation)