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Nicolas A. Belforte, Pablo Sande, Monica Chianelli, Ruth E. Rosenstein; Brief Pulses Of Ischemia Protect The Retina From Glaucomatous Damage. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3077.
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Glaucoma is a neurodegenerative disorder which is triggered by different factors including mechanical stress due to increased intraocular pressure (IOP), glutamate excitotoxicity, oxidative stress, and ischemia and reperfusion injury, among others. Retinal ischemia impairs retinal neuronal energy metabolism, by launching a reactions cascade resulting in cell death. Although there is no effective treatment against retinal ischemic injury, it is possible to activate an endogenous protection mechanism (ischemic tolerance) by ischemic preconditioning (IPC) or postconditioning (PostC). We investigated the effect of a weekly application of brief retinal ischemia pulses (ischemic conditioning) on retinal damage provoked by experimental glaucoma induced by weekly injections of chondroitin sulphate (CS).
Weekly bilateral injections of CS were performed in the eye anterior chamber of male Wistar rat for 10 weeks. Retinal ischemia was induced by increasing IOP to 120 mmHg for 5 min; this maneuver started 6 weeks after a weekly treatment with CS, and was weekly repeated in one eye while the contralateral eye was submitted to a sham procedure. At 10 weeks of treatment with CS, IOP was assessed with a TonoPen XL, ERGs were registered under scotopic conditions, and flash visual evoked potentials (VEPs) were registered with skull-implanted electrodes, while retinal morphology was examined by optical microscopy and immunohistochemistry (with an anti NeuN-antibody). Thiobarbituric acid reactive substances (TBARS) levels were measured as an index of lipid peroxidation.
Brief ischemia pulses, which did not affect the increase in IOP induced by CS, reversed the effect of chronic ocular hypertension on ERG and VEPs. Moreover, a significant preservation in the number of NeuN positive retinal ganglion cells was observed in the retina from hypertensive eyes exposed to ischemia pulses. An increase in lipid peroxidation was observed in the retina form eyes injected with CS, whereas ischemia pulses decreased this parameter.
These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies in glaucoma treatment.
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