The Role of Vitamin D in Uveitis: Immunological Mechanisms, Clinical Evidence, and Therapeutic Potential

Uveitis comprises a heterogeneous group of intraocular inflammatory disorders and remains a significant cause of visual impairment worldwide. Non-infectious uveitis is predominantly immune mediated, characterized by dysregulated innate and adaptive immune responses, breakdown of ocular immune privilege, and recurrent or chronic inflammation. Despite advances in immunosuppressive therapy, long-term disease control remains challenging, highlighting the need to identify additional modulatory factors in disease pathogenesis. Vitamin D has emerged as an important immunoregulatory hormone beyond its classical role in calcium homeostasis. It influences both innate and adaptive immunity through effects on antigen-presenting cells, T-cell differentiation, cytokine production, and immune tolerance. The expression of vitamin D receptors in immune and ocular tissues provides a mechanistic basis for its potential role in inflammatory eye disease. Experimental studies demonstrate that vitamin D signaling can attenuate ocular inflammation, suppress Th1 and Th17 responses, and reduce pro-inflammatory cytokine expression. Clinical observational studies generally report a high prevalence of vitamin D deficiency in uveitis, with associations between lower vitamin D levels and increased disease activity or recurrence. However, interventional evidence remains limited. Overall, vitamin D represents a biologically plausible but unproven factor in uveitis, warranting further investigation in well-designed clinical trials.