Vitamin D: Implications for ocular disease and therapeutic potential

Abstract

Vitamin D is a multifunctional hormone that is now known to play a significant role in a variety of biological functions in addition to its traditional role in regulating calcium homeostasis. There are a large number of studies demonstrating that adequate vitamin D levels are important in maintaining health and show that vitamin D is able to be utilized at local tissue sites. In the eye, we have increasing evidence of the association between disease and vitamin D. In this narrative review, we summarize recent findings on vitamin D and its relationship to various ocular pathologies and the therapeutic potential for some of these, as well as examine the basic science studies that demonstrate that vitamin D is biologically relevant in the eye.

Keywords: Anti-inflammatory; Deficiency; Genetic variations; Ocular disease; Vitamin D.

Figure 1

Vitamin D₃ production and activation. UVB from sunlight penetrates the skin, converting a cholesterol precursor, 7-dehydrocholesterol (7-DH), to pre-vitamin D₃ (pre-D₃), which then isomerizes to form vitamin D₃ (D₃). Recent evidence suggests that ocular surface cells also produce vitamin D₃ de novo when exposed to UVB. Vitamin D₃ must undergo two enzymatic steps to form the biologically active hormone. The skin, and possibly the cornea, is able to activate and utilize vitamin D₃ locally. However, the majority of vitamin D₃ is transported to the liver, where the 25-hydroxylases (25-OHase) CYP2R1 and CYP27A1, catalyze the formation of 25-hydroxyvitamin D₃ (25D₃), the major circulating form. Activation of 25D₃ traditionally occurs in the kidney through the 1α-hydroxylase, CYP27B1 (1α-OHase), although many extra-renal tissues and cell types are also able to activate 25D₃, including cells of the eye. The functionally active 1α-dihydroxyvitamin D₃ (1,25D₃) then binds to its nuclear hormone receptor, VDR, in target cells, influencing gene transcription through interactions with vitamin D response elements (VDRE).