Alpha lipoic acid attenuates the long-term effects of lead exposure in retinal ischemic injury mouse model

Lead (Pb) exposure is reported to be unsafe for humans. There have been several studies documenting acute and chronic Pb toxicity on the organ systems. New studies suggest that early-life exposure to such environmental toxins may increase the susceptibility to late-onset degenerative disorders. We aimed to examine the long-term effects of early-life postnatal exposure of Pb on retinal degeneration. Pb exposure (200 ppm) was provided either at postnatal day 1 through lactation (early-life exposure) or at 7th week of age (adulthood exposure) directly through drinking water for 20 days. The Pb-treated mice were followed till 20 weeks of age. At 20th week, ischemia/reperfusion (I/R) injury was induced in these mice by pterygopalatine artery ligation. Further, alpha lipoic acid (ALA) was administered to examine its neuroprotective effects against retinal damage. Histological and molecular analysis revealed that Pb-treated mice had greater retinal damage after I/R injury as compared to untreated or ALA treated mice, suggesting that ALA protects the early-life Pb exposure and its consequent impact on later life. The elevated levels of glial derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) and reduced levels of glial fibrillary acidic protein (GFAP) upon ALA pre-treatment suggest that it probably exerts anti-inflammatory effects via upregulation of neurotrophic factors.