Functional dichotomy: glutathione and vitamin E in homeostasis relevant to primary open-angle glaucoma

Abstract

Primary open-angle glaucoma (POAG) is a complex chronic neurological disease that can result in blindness. The goal of understanding the aetiology of POAG is to be able to target effective treatment to individuals who will eventually go blind without it. Epidemiological studies of POAG have not specifically addressed the possibility that nutrition may play a role in the development of POAG. A handful of papers have considered that nutrition may have an impact on POAG patients. POAG is not believed to be a ‘vitamin-deficiency disease’. The concept of ‘vitamin-deficiency diseases’ and the recommended daily allowances have not kept pace with the growing understanding of the cellular and molecular functions of vitamins and other micronutrients. The aetiology of POAG remains a mystery. Discoveries in cell physiology can be assimilated from the literature and applied to known homeostatic mechanisms of the eye. In this way the possible roles of nutritional components involved in the aetiology of POAG can be described. The mechanisms may be subject to many influences in ways that have yet to be defined. Two distinct changes in the trabecular meshwork can be identified: trabecular meshwork changes that cause intra-ocular pressure to increase and trabecular meshwork changes that are directly correlated to optic nerve atrophy. Compelling evidence suggests that collagen trabecular meshwork extracellular matrix (ECM) remodelling is correlated to increased intraocular pressure in POAG. Elastin trabecular meshwork ECM remodelling is correlated to POAG optic nerve atrophy. There appear to be two different pathways of ECM remodelling and apoptosis induction in POAG. The pathway for collagen remodelling and apoptosis induction seems to be exogenously influenced by water-soluble antioxidants, for example, glutathione. The pathway for elastin remodelling and apoptosis induction seems to be influenced by endogenous lipid-soluble antioxidants, for example, vitamin E. Roles can be defined for antioxidants in the two different pathways of ECM remodelling and apoptosis induction. This suggests that antioxidants are important in maintaining cellular homeostasis relevant to the aetiology of POAG.