Abstract
Age-related macular degeneration (AMD), the most common visual disorder in elderly people, is characterized by the formation of deposits beneath the retinal pigment epithelium (RPE) and by dysfunction of RPE and photoreceptor cells. The biologically active form of vitamin D, 1,25-(OH)2D3 (VITD), is categorized as a multifunctional steroid hormone that modulates many transcriptional processes of different genes and is involved in a broad range of cellular functions. Epidemiological and genetic association studies demonstrate that VITD may have a protective role in AMD, while single nucleotide polymorphisms in the vitamin D metabolism gene (CYP24A1) increase the risk of AMD. However, the functional mechanisms of VITD in AMD are not fully understood. In the current study, we investigated the impact of VITD on H(2)O(2)-induced oxidative stress and inflammation in human RPE cells. We demonstrate that exposure to H(2)O(2) caused significantly reduced cell viability, increased production of reactive oxygen species (ROS), lowered expression of antioxidant enzymes and enhanced inflammation. VITD exposure notably counteracted the above H(2)O(2)-induced effects. Our data suggest that VITD protects the RPE from oxidative damage and elucidate molecular mechanisms of VITD deficiency in the development of AMD.