Molecular Mechanisms Underlying the Therapeutic Role of Vitamin E in Age-Related Macular Degeneration

Abstract

The eye is particularly susceptible to oxidative stress and disruption of the delicate balance between oxygen-derived free radicals and antioxidants leading to many degenerative diseases. Attention has been called to all isoforms of vitamin E, with α-tocopherol being the most common form. Though similar in structure, each is diverse in antioxidant activity. Preclinical reports highlight vitamin E’s influence on cell physiology and survival through several signaling pathways by activating kinases and transcription factors relevant for uptake, transport, metabolism, and cellular action to promote neuroprotective effects. In the clinical setting, population-based studies on vitamin E supplementation have been inconsistent at times and follow-up studies are needed. Nonetheless, vitamin E’s health benefits outweigh the controversies. The goal of this review is to recognize the importance of vitamin E’s role in guarding against gradual central vision loss observed in age-related macular degeneration (AMD). The therapeutic role and molecular mechanisms of vitamin E’s function in the retina, clinical implications, and possible toxicity are collectively described in the present review.

Vitamin K and the Visual System: A Narrative Review

“…It is well established that the fat-soluble vitamins (FSV) A, D, and E play essential roles, and in some cases can have toxic effects, in the eye and visual system [227][228][229]. Vitamin A in the form of 11-cis-retinal is indeed the singular light sensitive molecule setting in motion the visual cycle resulting in the transduction of photons into nervous impulses [228], and its deficiency has been heralded by night blindness and xerophthalmia for millennia-the direct result of which lead to its discovery as the first FSV [125].…”

“…Vitamin A in the form of 11-cis-retinal is indeed the singular light sensitive molecule setting in motion the visual cycle resulting in the transduction of photons into nervous impulses [228], and its deficiency has been heralded by night blindness and xerophthalmia for millennia-the direct result of which lead to its discovery as the first FSV [125]. Vitamins D [227] and E [229], likewise have been shown to have pleotropic benefits as well as rare toxicity for the EVS, with toxic levels of A, D, and E, unlike VK, able to accumulate within the body [230].…”

Role of Oxidative Stress in Ocular Diseases: A Balancing Act

“…However, the follow-up clinical study, called the Age-Related Eye Disease Study 2 (AREDS2), testing the effects of further supplementation with omega-3-fatty acids DHA and EPA, along with carotenoids, lutein, and zeaxanthin, indicated no further reduction in AMD progression [ 276 ]. Supplementation with compounds such as Vitamin E, which has the ability to inhibit lipid peroxidation [ 277 ], has also shown protective properties in the RPE. Alpha-tocopherol transfer protein (α-TTP) has been associated with the maintenance of serum Vitamin E levels.…”

The Importance of Natural Antioxidants in Female Reproduction

“…Vitamin E exists in eight isoforms, from which the α-tocopherol is the most effective form and γ-tocopherol is the most common [ 73 ]. This naturally occurring fat-soluble vitamin acts as a scavenger of peroxyl radicals in cell membranes (affects the stability of the membrane and indirectly modulates the signaling properties of membrane proteins) and terminates lipid peroxidation chain reactions [ 73 ]. After the reaction with lipid peroxyl radical, a stable tocopherol radical is formed which undergoes reverse conversion to α-tocopherol ensured by ascorbic acid or glutathione GSH [ 74 ].…”