Vitamin A, systemic T-cells, and the eye: Focus on degenerative retinal disease

Abstract

The first discovered vitamin, vitamin A, exists in a range of forms, primarily retinoids and provitamin carotenoids. The bioactive forms of vitamin A, retinol and retinoic acid, have many critical functions in body systems including the eye and immune system. Vitamin A deficiency is associated with dysfunctional immunity, and presents clinically as a characteristic ocular syndrome, xerophthalmia. The immune functions of vitamin A extend to the gut, where microbiome interactions and nutritional retinoids and carotenoids contribute to the balance of T cell differentiation, thereby determining immune status and contributing to inflammatory disease around the whole body. In the eye, degenerative conditions affecting the retina and uvea are influenced by vitamin A. Stargardt’s disease (STGD1; MIM 248200) is characterised by bisretinoid deposits such as lipofuscin, produced by retinal photoreceptors as they use and recycle a vitamin A-derived chromophore. Age-related macular degeneration features comparable retinal deposits, such as drusen featuring lipofuscin accumulation; and is characterised by parainflammatory processes. We hypothesise that local parainflammatory processes secondary to lipofuscin deposition in the retina are mediated by T cells interacting with dietary vitamin A derivatives and the gut microbiome, and outline the current evidence for this. No cures exist for Stargardt’s or age-related macular degeneration, but many vitamin A-based therapeutic approaches have been or are being trialled. The relationship between vitamin A’s functions in systemic immunology and the eye could be further exploited, and further research may seek to leverage the interactions of the gut-eye immunological axis.

Nutritional Factors: Benefits in Glaucoma and Ophthalmologic Pathologies

“…Vitamin A is an ancient treatment for nutritional blindness, including for cases of xerophthalmia, keratomalacia, and the ocular manifestation of hypovitaminosis A. Dietary supplementation and fortification are recommended to retard the widespread prevalence of vitamin A deficiency [ 238 ]. Studies have recommended that vitamin A could be useful for managing retinal degenerative diseases such as age-related macular degeneration and Stagardt’s disease [ 239 ]. Vitamin A can also been found in several oral supplements together with other substances in the management of glaucoma.…”

Microbial Dynamics in Ophthalmic Health: Exploring the Interplay between Human Microbiota and Glaucoma Pathogenesis

“…While carotenoid supplementation has shown positive effects on visual performance in ABCA4-knockout mice, no clinical trials involving nutritional interventions have been conducted thus far. In fact, there are contradictory findings regarding the impact of dietary vitamin A on STGD outcomes, with some laboratory research indicating that vitamin A supplementation may lead to an increased accumulation of lipofuscin (albeit without significant effects on retinal function), and thus, recommend that STGD patients avoid retinoid supplements [87,88].…”

Novel Approaches in the Drug Development and Delivery Systems for Age-Related Macular Degeneration

“…The mechanism of action of these modulators includes supplementing with deuterated vitamin A, suppression of visual cycle enzymes, the inhibition of retinol-binding protein 4 (RBP4), and scavenging free all-trans-RAL [ 44 ]. Visual transduction is coordinated by vitamin A in the body, but the higher accumulation of vitamin A dimers is reported to be associated with the development of AMD [ 45 ]. A synthetic deuterated vitamin A formulation (ALK-001) was proposed for replacing the vitamin A in the body and slowing down the disease progression [ 46 ].…”