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C.M. Hamilton, K.J. Powell, C.A. B. Jollimore, M.E. M. Kelly; Effect of Minocycline on RGC Survival and Astrogliosis in a Rat Model of Elevated Intraocular Pressure . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1572.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the effects of minocycline, a second generation tetracycline antibiotic with reported retinal neuroprotective properties, on RGC apoptosis and astrogliosis in an acute rat model of elevated intraocular pressure.
Intraocular pressure was increased to 110 mmHg for 60 minutes in the experimental eye of adult male Long Evans rats. The other eye served as a control. Rats were given daily i.p. injections of either 0.9 % NaCl or a 45 mg/kg loading dose of minocycline for three days preceding the ischemic insult. Injections were administered for up to 2 weeks following ischemia, with a maintenance dose of minocycline of 22.5 mg/kg. RGCs in retinal whole–mounts from control and experimental eyes in saline– and minocycline–treated animals were visualized by retrograde labeling with fluorogold (FG). Apoptosis was further determined using Western Blotting to quantify protein for pro–apoptotic caspase–3. Alterations in glial fibrillary protein (GFAP), a specific marker for activated astrocytes, were examined using Western Blotting and immunohistochemistry in retinal sections from the control and experimental eyes of saline– and minocycline–treated animals.
The number of FG–positive RGCs was increased in the experimental eyes of minocycline–treated animals compared to saline–treated animals at 14 days post ischemia (71% of control eye in saline–treated and 86% in minocycline–treated animals, n=3). Caspase–3 protein was increased to 124% of control eyes in the experimental eyes of saline–treated animals with no increase apparent between control and experimental eyes in minocycline–treated animals. Glial fibrillary protein was increased to 112% of control in the experimental eyes of saline–treated animals and to 128% of control in minocycline–treated animals. Immunohistochemical examination of GFAP expression in retinal sections revealed labelling of Mueller cells with increased expression in experimental eyes compared to control eyes in both saline– and minocycline–treated animals.
Minocycline appears to be neuroprotective against RGC loss for up to 14 days post ischemic insult. Consistent with the increase in RGC survival, expression of pro–apoptotic caspase–3 protein is reduced in the experimental eyes of minocycline–treated animals compared to saline–treated animals. Minocycline did not prevent the increase in GFAP protein seen in experimental eyes, suggesting that minocycline does not prevent astrogliosis in post–ischemic retina.
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