Minocycline Partially Inhibits Caspase-3 Activation and Photoreceptor Degeneration after Photic InjuryChang C.-J.a, c · Cherng C.-H.c · Liou W.-S.b · Liao C.-L.d
Departments of aOphthalmology and bPharmacy Practice, Tri-Service General Hospital, Taipei; Departments of cMedical Sciences and dMicrobiology and Immunology, National Defense Medical Center, Taipei, Taiwan, ROC
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Purpose: To evaluate the possible role of caspase-3 in retinal photic injury, and to investigate whether minocycline can ameliorate light-induced photoreceptor degeneration. Methods: Retinal photic injury was induced in rats by exposure to intense light. Expression of caspase-3 was studied using Western blot analysis, immunohistochemical staining and enzyme activity assay. Apoptotic photoreceptor cells were detected by the TdT-dUTP terminal nick-end labeling (TUNEL) method. Minocycline (15, 30 or 45 mg/kg) was administered before or after photic injury in rats randomly assigned to pretreatment and posttreatment groups. Minocycline and vehicle-treated retinas subjected to photic injury were compared with respect to Western blotting, enzyme activity assay, quantitative counts of TUNEL stains, morphometry of the outer nuclear layer (ONL) thickness and histopathological examination. Results: After light exposure, active caspase-3 and poly-adenosine diphosphate-ribose-polymerase were upregulated in the retinas and increased caspase-3 immunoreactivity was observed in the ONL. Caspase-3 enzyme activity increased in the retinas that underwent photic injury, and this increase was significantly reduced in minocycline pretreated (30 and 45 mg/kg) and posttreated (45 mg/kg) groups. Intraperitoneal administration of minocycline before or after photic injury in rats also resulted in less TUNEL-positive photoreceptors, as assessed by the quantitative TUNEL counts. The degree of retinal degeneration, measured by the ONL thickness 14 days after photic injury, was significantly improved in minocycline pretreatment (45 mg/kg) rats. Conclusions: We demonstrate that increased caspase-3 activities localize specifically within the ONL after photic injury, and that minocycline partially inhibits caspase-3 activation and photoreceptor degeneration in this animal model.
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