The Role of Vitamin D in Noninfectious Uveitis: A Scoping Review with Transcriptomic and Bioinformatic Insights

Vitamin D deficiency has been linked to immune dysregulation and increased risk of autoimmune diseases, including noninfectious uveitis (NIU). This study synthesized evidence linking vitamin D metabolism-related genes and immune mechanisms to NIU and explored transcriptomic pathways potentially modulated by vitamin D signaling.

A scoping review of clinical, genetic, and experimental studies evaluating vitamin D status, vitamin D-related polymorphisms, and immunological mechanisms in NIU was conducted following PRISMA-ScR guidelines. In parallel, transcriptomic data from the Gene Expression Omnibus were analyzed using Gene Set Enrichment Analysis to identify immune and inflammatory pathways enriched in NIU subtypes versus healthy controls, focusing on vitamin D signaling and innate immune activation.

The review identified consistent associations between hypovitaminosis D and increased risk or severity of NIU across subtypes, including Behçet disease-associated uveitis and HLA-A29-positive birdshot chorioretinopathy. Genetic studies associated NIU susceptibility with polymorphisms in vitamin D metabolism and signaling genes, including DHCR7, GC/VDBP, CYP27B1, and VDR. Transcriptomic analysis revealed enrichment of innate immune and inflammatory pathways, including Toll-like receptor and MyD88-dependent signaling, tumor necrosis factor-related pathways, oxidative stress responses, and dysregulation of immunoregulatory mediators such as interleukin-10, particularly in immune-mediated NIU phenotypes.

Integrating scoping review findings with transcriptomic analyses supports a multifactorial relationship between vitamin D status, genetic susceptibility, and immune pathway dysregulation in NIU. Although causality cannot be established, vitamin D deficiency may represent a potentially modifiable factor influencing innate and adaptive immune responses. Prospective and interventional studies are warranted to determine whether vitamin D supplementation can modify disease activity or clinical outcomes.