Mechanisms of ocular neuroprotection by antioxidant molecules in animal models

This work was conducted to evaluate the efficacy of a treatment on retinal ganglion cells (RGC) and on astrocytes of the optic nerve of glaucomatous eyes, using a combination of alpha-lipoic acid (ALA) and superoxide dismutase (SOD). Thirty-two male Wistar rats were fed with a diet supplemented with ALA, SOD, ALA and SOD or with no product for 8 weeks. Ocular hypertension was induced with 2% methylcellulose (MTC) and then rats were sacrificed. TUNEL assay showed a marked fluorescence in the ganglion cells and astrocytes of MTC-treated rats evidencing induction of apoptosis. In contrast, sections of eyes pretreated with ALA and SOD showed a lack of fluorescence quite similar to that of the controls. Similarly, eyes sections from rats pre-treated with ALA and SOD showed reduced differential expression of inducible nitric oxide synthase (iNOS) and of caspase-3 in compared to normally-fed/MTC-inoculated cases. An increase of ALA and SOD exerts an antiapoptotic effect and protects against oxidative stress and hence against the structural remodelling of the RGCs and astrocytes of the optic nerve in the presence of an ischemic and pressure stress.