High levels of glucocorticoids participate in retinal degeneration induced by continuous illumination.

LK. JULIÁN, EM. LÓPEZ, H. COIRINI, JJ. LÓPEZ

Fort Lauderdale, USA

Congreso; Annual Meeting of the Association for Research in Vision and Ophthalmology,; 2004

ARVO

Glucocorticoids (GC) exert a deletereous action on hippocampal CA3 neurons which may be avoided by surgical or pharmacological adrenalectomy. However, little is known about the effects of GC on the retina. The oxidative stress produced by continuous illumination induces retinal degeneration of photoreceptors. This stressful exposure induces an increase of GC levels which may be involved in light induced retinal damage. In order to verify this hypothesis, fifteen Sprague Dawley rats were adrenalectomized under Ketamine anesthesia (50 mg/kg, IP) following ARVO Guidelines of Animal Use Statement. After eighteen hours of recovery; adrenalectomized (ADX) and intact control animals (CTL) were submitted to continuous illumination (10000 lux) up to 7 days. Animals were offered water (CTL) or saline solution (NaCl, 0.9%) (ADX) and food ad libitum. Rats were anesthetized with chloral hydrate (350 mg/kg, IP) and sacrifized either before or after 1, 2, 5 and 7 days of continuous illumination. Eyes were removed and fixed by immersion in 4% paraformaldehyde solution. Cryostat sections were stained with hematoxiline-eosine and retinal thickness was determined with a Kontron-Vidas image analyzer connected to an optical microscope. Data were statistically analyzed using the Student Newman-Keuls Multiple comparison test. Although there were not differences between CTL and ADX retinas before illumination, after 24 hs of continuous illumination retinas of ADX rats were significantly thicker than CTL retinas (196,18±14,41 ìm vs 129,97±19,34 ìm, p<0,001). Dense picnotic nuclei were observed in the outer nuclear layer (ON) of CTL and ADX illuminated retinas. Photoreceptors segments were damaged in CTL retinas, but they were quite preserved in ADX retinas. After 7 days of illumination, an important degeneration of photoreceptors was observed in both, CTL and ADX rats. Cellular debris were observed between ON and retinal pigment epithelium (RPE), and vacuolar inclusions, compatible with lipofucsin, were detected in RPE. An important number of ON nuclei showed irregular boundaries and nuclear fragmentation compatible with apoptosis. However retinal thickness of ADX vs CTL rats was 73,36 ±12,62 ìm vs 55,64 ±5,71 ìm (p<0,001). The present results suggest that a high level of GC may be a collaborative factor in light induced retinal damage. The effect of GC must be taken in account in degenerative diseases of the retina (Supported with grants from UBA and CONICET, UBACYT-M047 and PIP 819/98).