In the news:Meta-analysis Links Vitamin D & DED; Vitamin B3 for Fibrotic Eye Disease?

Potential Vitamin D Mechanisms in DED

Studies have begun to shed light on the potential role of Vitamin D in the development of dry eye disease. An underlying cause of DED is inflammation which appears as discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. There is evidence that the immune and anti-inflammatory effects of vitamin D might influence DED by regulating the production of pro-inflammatory cytokine IL-17 and anti-inflammatory IL-6.

Vitamin D could also affect ocular pain or discomfort through modulating nociception. There are several theories about the mechanism linking vitamin D to pain. Serotonin, which can extend chronic pain response, has been shown to be high in subjects with DED. Vitamin D is known to affect serotonin synthesis. Additionally, vitamin D could modulate pain by decreasing nitric oxide, a nociceptive neurotransmitter.

Another mechanism proposed for a beneficial effect of vitamin D in DED is its ability to improve corneal epithelial barrier function. The epithelium of the ocular surface functions as a barrier to the penetration of harmful substances into the cornea and maintains ocular surface integrity.

Yet despite the progress made in understanding the mechanistic connections between this vitamin and DED, studies examining the relationship of vitamin D status to DED have not been consistent.

Systematic Review and Meta-Analysis Results

To address this issue, researchers conducted a systematic review and meta-analysis of observational studies evaluating the association between serum vitamin D and DED in patients as compared to healthy adult subjects(1).

A total of 14 studies out of 252 met the inclusion criteria and were included in the review and analysis. Serum 25(OH) D3 was lower in dry eye disease subjects compared to healthy ones (p<0.001). Vitamin D was also associated with the results of the Ocular Surface Disease Index score (p=0.043). No association, however, was found between serum vitamin D and tear break-up time (TBUT) and Schirmer’s test results.

According to the authors, this finding was in line with previous observational studies, though a previous intervention study reported a beneficial impact of supplemental vitamin D on TBUT and Schirmer’s.

Vitamin B3 for Fibrotic Eye Diseases?

A study reporting that vitamin B3 (nicotinamide form) may improve inner retinal function in those with glaucoma was summarized in a recent EduFacts (see SBH.com). From researchers at Mt. Sinai Hospital comes a new study that suggests vitamin B3 can inhibit aggressive cell trans-formations during wound healing(2)(3).

According to a Mt. Sinai statement, the findings apply to a condition in which cells in the retinal pigment epithelium, a layer that supports the retina, transform and develop the characteristics of more aggressive cells known as mesenchymal cells. The condition can be triggered by aging, diabetes, or eye injury. This causes development of fibrous membranes that resemble damaging cells found in retinal scar tissue and leads to retinal detachment. (https:/www.mountsinai.org/about/newsroom/2020/researchers-find-that-nicotinamide-may-help-treat-fibrotic-eye-diseases-and-mitigate-vision-pr)

Testing the vitamin in human cells, the investigators found that vitamin B slowed down the aggressive cellular transformation. It could also promote the opposite transition, from mesenchymal to epithelial, helping to preserve the cell’s original identity.

The findings may be key to the development of therapies to treat fibrotic eye disease. Diseases such as AMD, diabetic retinopathy and neovascular glaucoma have in common the final pathological denominator of chronic wound healing leading to fibrosis.

References

1. Askaria G, et al. Association between vitamin D and dry eye disease: A systematic review and meta-analysis of observational studies. Contact Lens and Anterior Eye. 43:418–425
2. Boles NC, et al. Epigenomic and transciptomic changes during human RPE EMT in a stem cell model of epiretinal membrane pathogenesis and prevention by ncotinamide, Stem Cell Reports. 14: 631–47, 2020.