Calpains are activated by light but their inhibition has no neuroprotective effect against light-damage.
Calpain had been shown to be highly activated at one day after exposure to the damaging light (Perche et al. (2007)Caspase-dependent apoptosis in light-induced retinal degeneration. Invest Ophthalmol Vis Sci 48:2753-2759.), suggesting that they might play a critical role in photoreceptor apoptosis induced by light. Therefore in the present study we investigate the role of calpain in light-induced photoreceptor cell death. In a first set of experiments, untreated albino Wistar rats were sacrificed at 0, 2, 4, 6, 12, 24 h of light exposure and at one day after the light was turned off (D1) to measure retinal calpain activity and to study calpain expression. In a second set of experiments, after control electroretinograms (ERGs), rats were uninjected or injected intravitreally with DMSO or the calpain inhibitor Mu-Phe-hPhe-FMK, before being exposed to the damaging light for 24 h. ERGs were then recorded at one day (D1) and fifteen days (D15) after the end of light exposure. Rats were sacrificed at D1 for apoptotic cell detection or D15 for histological analysis (ONL thickness). Calpain activity and expression significantly increased in Untreated retinas, from 0 h to D1. DMSO has no effect on calpain activity. Mu-Phe-hPhe-FMK significantly inhibited retinal calpain activity by 85% at 2 h of light exposure and still 48% at D1. However, Mu-Phe-hPhe-FMK has no effect on light-induced retinal degeneration as evidence by equivalent loss of function, equivalent loss of photoreceptor cells and an equivalent number of apoptotic cells in Mu-Phe-hPhe-FMK and DMSO retinas. Therefore, calpains are up-regulated by light stress but they do not have a pivotal role in photoreceptor apoptosis.
Perche
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Univ Clermont 1, UFR Pharmacie, Laboratoire de Biophysique Sensorielle, EA 2667, 28, place Henri Dunant-B.P. 38, 63001 Clermont-Ferrand, France. olivier.perche@u-clermont1.fr
Doly
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M
Ranchon-Cole
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004151:Dipeptides / Q000494:pharmacology / Q000627:therapeutic use; D004596:Electroretinography / Q000528:radiation effects; D008027:Light / Q000009:adverse effects*; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010775:Photic Stimulation / Q000379:methods; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control
D002135:Calcium-Binding Proteins; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D009025:Morpholines; D018696:Neuroprotective Agents; C080182:P 34081; C033668:calpastatin; D002154:Calpain