Alpha-lipoic acid: A possible pharmacological agent for treating dry eye disease and retinopathy in diabetes

Alpha-lipoic acid (ALA) is a naturally occurring dithiol micronutrient which acts as a cofactor for mitochondrial enzyme activity. Due to its potential antioxidant activity, it is considered as "universal antioxidant". Previous studies reported the pharmacological benefits of ALA such as glycaemic control, improved insulin sensitivity and alleviation of diabetic complications such as neuropathy and cardiovascular diseases. Dry eye disease and retinopathy are prevalent in diabetic patients. Experimental studies demonstrated the beneficial effects of ALA in dry eye and diabetic retinopathy. ALA can prevent the dry eye by down regulating the expression of matrix metalloproteinase-9 in the corneal epithelial cells and activating the antioxidant status of the ocular surface. Furthermore, its direct antioxidant effect can also prevent oxidative stress-induced corneal surface erosion and lachrymal gland damage. ALA prevents diabetic retinopathy through inhibition ofO-linked beta-N-acetylglucosamine transferase and nuclear factor-kappa B activity and alleviation of oxidative stress. It can activate the nuclear factor erythroid-2-related factor 2 and AMP-activated protein kinase in retinal ganglion cells. Clinical trials conducted in pre-retinopathic diabetic patients showed ALA with genistein and vitamins could protect the retinal cells and decline the inflammatory effect in diabetic patients. However, studies are scant to explore its beneficial effects in dry eye disease and diabetic retinopathy. Therefore, this review article discusses an update on the role of ALA in dry eye disease and diabetic retinopathy, two ocular diseases prevalent in diabetic patients.