Role Of Vitamin D Receptors In Corneal Health And Disease

Vitamin D (VD) – Vitamin D receptor (VDR) axis is crucial in facilitating physiological endogenous anti-inflammatory regulation in various cells and tissues, including the ocular surface. Aberrant levels of inflammatory factors have been observed on the ocular surface of patients with dry eye disease (DED) or keratoconus (KC). VD deficiency is in very prevalent among the population and is very significant contributor to disease pathogenesis. Hence, this study investigates the expression status of ocular surface VDR in DED patients and effect of VD supplementation on the ocular surface of KC patients.

Tertiary Eye care Hospital

Expression of VDR was determined in conjunctival impression cytology (IC) samples in controls (n=11) and DED patients (n=15) by quantitative PCR (qPCR) along with inflammatory factors including IL-6 and MMP9. Expression of VDR was also studied in human corneal epithelial cells (HCE) under in vitro hyperosmotic stress with or without calcitriol (active form of VD) and genistein (isoflavone). KC patients (n=x) with VD deficiency were recruited for the study. Corneal parameters (topography, pachymetry) along with expression status of lysyl oxidase (LOX, endogenous collagen cross-linking agent) and collagens were determined (via quantitative PCR from corneal and conjunctival IC samples) before and after systemic VD supplementation

The expression of VDR was significantly lower along with a significant increase in IL-6 and MMP9 on the ocular surface of DED patients. Hyperosmotic stress significantly reduced the expression of VDR and increased the expression of inflammatory factors in HCE. Calcitriol-Genistein combination rescued hyperosmotic stress induced degradation of VDR in HCE and along with reduced expression of inflammatory factors. There were no detrimental changes in the corneal parameters of KC patients between the two visits. In addition, a significant increase in the expression of LOX, Collagen 1A1 and Collagen 4A1 were observed in cornea and conjunctiva following VD supplementation compared to pre-treatment levels in KC patients.

The findings suggest the disruption of a physiologically relevant VD-VDR axis on the ocular surface of DED patients and strategies to restore it. The beneficial ocular surface effects of VD supplementation in the KC patients. Hence, VDR activation and vitamin D supplementation can be explored as a novel strategy in DED and KC management.