Extra-renal synthesis of vitamin D3 has been reported in many tissues and cells including barrier sites where it induced immunomodulatory effects. I investigated local synthesis of vitamin D3 and its role in the induction of host defense peptides (HDPs) in human ocular barrier epithelial cells. I also examined the association between vitamin D receptor (VDR) single nucleotide polymorphism (SNP) with intermediate uveitis (IU) in Caucasians. Human corneal endothelial (HCEC-12), non-pigmented ciliary body epithelial (ODM-2), and adult retinal pigment epithelial (ARPE-19) cell lines, expressed mRNA and protein for VDR and vitamin D3 pathway elements and can locally synthesise 1,25(OH)2D3 in vitro. These cells upregulated mRNA, but not protein expression of HDPs in response to vitamin D3. IL-1β and TNF-\(\alpha\) did not synergise with vitamin D3 to upregulate HDPs in ocular barrier epithelial cells. VDR single nucleotide polymorphisms BsmI (rs1544410) is significantly associated with IU. Allele rs1544410-T and genotype rs1544410-CT were higher in IU patients than healthy controls. The results show that that extra-renal production of active vitamin D3 occurs in ocular barrier cells and may contribute to immune regulation in the eye. The association with SNP in the vitamin D3 receptor gene and intermediate uveitis suggests that genetic control of vitamin D3 may be linked to ocular inflammatory disease.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:573526 |
| Date | January 2013 |
| Creators | Alsalem, Jawaher Abdullah |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/4243/ |
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