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Review
. 2017 Oct 13;9(10):1120.
doi: 10.3390/nu9101120.

Vitamin D and Age-Related Macular Degeneration

Alfredo Garcia Layana  1 , Angelo Maria Minnella  2 , Gerhard Garhöfer  3 , Tariq Aslam  4   5 , Frank G Holz  6 , Anita Leys  7 , Rufino Silva  8   9   10   11 , Cécile Delcourt  12 , Eric Souied  13 , Johanna M Seddon  14   15
Affiliations
Review

Vitamin D and Age-Related Macular Degeneration

Alfredo Garcia Layana et al. Nutrients. .

Abstract

In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD). Its active metabolite, 1α,25-dihydoxy vitamin D, acts as a modulator of cell proliferation, differentiation and apoptosis, and cumulative data from experimental and observational studies suggest that relatively a lower vitamin D status could be a potential risk factor for the development of early and/or late AMD. Herein, we made a narrative review of the mechanisms linking a potential role of vitamin D with the current concepts of AMD pathophysiology.

Keywords: age-related macular degeneration; angiogenesis; inflammation; vitamin D.

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Conflict of interest statement

Laboratoires Théa, France funded the medical writing assistance and covered the publication costs, but had no role in the design of the study, in the collection, analysis, or interpretation of data. A.G.L.: Allergan, Bausch & Lomb, Laboratoires Théa, Bayer, Novartis and Roche. A.M.M.: Novartis, Laboratoires Théa; Travel expenses from Allergan, Bayer. G.G.: Consultant for Laboratoires Théa, Santen, Novartis, Redwood, Panoptes, Croma and Inotek. T.A.: Consultant to Novartis, Bayer, Laboratoires Théa Pharmaceuticals, Bausch & Lomb, Oraya. F.G.H.: Research support from Allergan, Bayer, Genentech, Heidelberg Engineering, Novartis, and Roche and consultant for Alcon, Bayer, Genentech, Heidelberg Engineering, Novartis, Roche, and Théa. A.L.: Speaker for Thea. R.S.: Member of Advisory Board for Alimera, Allergan, Alcon, Bayer, Novartis, Thea. C.D.: Consultant for Allergan, Bausch & Lomb, Laboratoires Théa, Novartis and Roche. J.M.S.: Novartis, Laboratoires Théa, Apellis and Gemini. E.S. declares no conflict of interest in relation with this research.

Figures

Figure 1
Figure 1
Metabolism of vitamin D. Vitamin D (ergocalciferol and/or cholecalciferol) is produced and excreted by basal skin keratinocytes exposed to ultraviolet radiation (UV-B), or directly provided by food. While skin vitamin D is transported into the liver bound to binding proteins (DBP), dietary vitamin D is absorbed by the gastro-intestinal tract and transported to the liver via the venous circulation and chylomicron remnants. Part of the vitamin D produced is stored in fat cells and may serve as an endogenous source of vitamin D. In the liver, vitamin D2 and vitamin D3 are hydroxylated in position 25 by several enzymes found in microsomal or mitochondrial fractions. Once produced in the liver, 25(OH)D is released into the bloodstream whilst bound to DBP. Alternatively, vitamin D can be metabolized in 25(OH)D in other tissues. In the kidney, 25(OH)D is converted to the active metabolite, 1,25(OH)2D, through the action of the enzyme 1-alpha-hydroxylase (CYP27B1), located in the proximal tubules. In excess, 1,25(OH)2D and 25(OH)D activate 24-hydroxylase (CYP24A1) and are degraded into 24-hydroxylated products, i.e., 24,25(OH)2D and 1,24,25(OH)3D, which have no biological activity. Once produced in the kidney, 1,25(OH)2D is released and transported into the bloodstream and is mainly bound to DBP until it reaches target tissues expressing the vitamin D receptor.
Figure 2
Figure 2
Major biological functions of vitamin D.
Figure 3
Figure 3
Main biological mechanisms in age-related macular degeneration (AMD) and putative vitamin D effects. Inhibitory activities of vitamin D (1,25(OH)2D) are indicated in green truncated arrows and mechanisms of AMD pathophysiology in red arrows. AMD is characterized by progressive degeneration of the macula, involving the retinal pigment epithelium (RPE), the Bruch’s membrane (BM), and alterations in choroidal capillaries (CC). Chronic oxidative stress in senescent RPE is a key event in maintaining macular damage and initiating early AMD. The release of cell debris and the accumulation of specific deposits (drusen) is the hallmark histopathological feature of eyes with early and intermediate AMD. Vitamin D may prevent the risk for developing early and intermediate AMD, by inhibiting oxidative stress, inhibiting extracellular amyloid deposits and inhibiting macrophage activation. Advanced dry AMD is characterized by atrophy of RPE cells and choriocapillaries. RPE dysregulation, due to oxidative stress and inflammatory reactions, may lead to abnormal angiogenesis, leading to neovascular AMD. Vitamin D may reduce the risk or slow the development of neovascular AMD by inhibiting angiogenesis or immune cell activation (see text for details).
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