# Vitamin D Metabolism and Function in the Cornea and Anterior Segment

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2020 · $401,610

## Abstract

Vitamin D (Vit D) insufficiency and deficiency is a significant health issue. Our lab has been conducting pioneering studies
examining the role of Vit D in the eye, with a focus on the cornea. Exciting emerging data point to the therapeutic potential
of Vit D in treating ocular pathologies. The general hypothesis is that Vit D deficiency or insufficiency can lead to
exacerbated anterior segment-related ophthalmic problems brought on by a primary insult or disease.
Specific Aim 1. Examine the influence of Vit D deficiency on corneal epithelial wound healing in diabetic mice.
Rationale. Diabetes is a significant complicating factor in any number of pathological conditions, and diabetic keratopathy
effects approximately 70% of all diabetics. The hypothesis for Aim 1, based on novel preliminary data collected using
diabetic VDR knockout mice, is that Vit D deficiency will lead to a significantly exacerbated deficit in the corneal wound
healing of diabetic mice.
Approach. Cornea epithelial wounds will be made in control and vitamin D receptor (VDR) knockout diabetic mice.
Healing rates will be compared and corneas will be examined for morphological differences. The influence of Vit D
metabolites on wound healing in these VDR knockout diabetic mice will be determined.
Specific Aim 2. Examine effects of 24,25D on corneal epithelial cell function.
Rationale. We previously demonstrated that the concentration of 24,25D is the highest of all Vit D metabolites in the eye.
Recent studies indicate that 24,25D is not just an inactive metabolite. Our preliminary studies demonstrate that 24,25D may
play a significant role in the function of the corneal epithelium.
Approach. The influence of 24,25D on corneal epithelial cell proliferation and migration will be studied using cell culture.
24,25D effects on the expression of VDR and the key Vit D metabolic-related enzymes CYP27B and CYP24A1 will be
measured using qPCR and western blotting. 24,25D signaling through VDR will be examined using VDR knockout mice
and cell culture. Integrated with Aims 1 and 3, respectively, we will examine the influence of 24,25D on corneal epithelial
wound healing along with gap junction function and desmosomes.
Specific Aim 3. Determine how Vit D influences corneal epithelial intercellular junctions.
Rationale. We previously demonstrated that Vit D influences the function of corneal epithelial gap junctions and tight
junctions. We will test the hypothesis, based on our preliminary studies, that the gap junction functional effects we reported
are directly related to modified density and distribution of specific gap junction proteins and that the weak epithelial
attachment we observe in VDR knockout mice is related to changes in desmosome protein density and distribution.
Approach. Determine the influence of VDR knockout on corneal epithelial mRNA levels, density, and distribution of gap
junction- and desmosome-specific proteins. We will also examine the influence of VDR knockout on corn...

## Key facts

- **NIH application ID:** 9893875
- **Project number:** 5R01EY021747-09
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** MITCHELL A WATSKY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $401,610
- **Award type:** 5
- **Project period:** 2012-05-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893875

## Citation

> US National Institutes of Health, RePORTER application 9893875, Vitamin D Metabolism and Function in the Cornea and Anterior Segment (5R01EY021747-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9893875. Licensed CC0.

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