Vitamin D and vitamin D receptor in patients with ophthalmic pterygium

Abstract

Pterygium, an ultraviolet radiation (UV)-related disease, is a relatively benign process, but since it displays tumor-like features, it has been proposed to be a neoplastic-like growth disorder. Vitamin D performs a number of functions in addition to calcium homeostasis, as inhibition of cell proliferation, activation of apoptotic pathways, and inhibition of angiogenesis. Since the antitumor actions of vitamin D are mediated primarily through the nuclear vitamin D receptor (VDR), the aim of the present study was to investigate vitamin D status in patients with pterygium and in control subjects, and VDR immunohistochemical expression in samples of pterygium and normal conjunctiva in order to evaluate a possible role of vitamin D pathway in the pathogenesis of the disease. Serum vitamin D concentration was measured among 41 patients with pterygium and 47 volunteers by an automated chemiluminescence immunoassay. Moreover, 23 formalin-fixed and paraffin-embedded pterygium biopsy samples and 24 conjunctiva\ud specimens were treated for the immunohistochemical demonstration of VDR using the streptavidin-biotin alkaline phosphatase method. No differences were observed about vitamin D level between patients with pterygium and control group, but significant differences between VDR immunolocalization in pterygium and normal conjunctiva\ud were observed (P=0.00001). In conjunctiva, the immunoreactivity, localized mainly in cytoplasm of epithelial cells, may probably demonstrate VDR regulation of cell growth, differentiation, and apoptosis, while in pterygium VDR co-localization in the nucleus and cytoplasm of epithelial cells may indicate alternative nuclear pathways by which vitamin D might exert its antiinflammatory and anti-proliferative effects by the regulation of gene expression

Association between Vitamin D Receptor Gene Polymorphisms and Periodontal Bacteria: A Clinical Pilot Study

“…The variant does not determine structural alterations of the protein, but the presence of the G allele (b) affects the polyadenylation of the transcript, influencing the stability of mRNA and therefore modifying the protein expression. However, several meta-analyses have only shown that the G (b) allele showed lower but not significant bone mass density values [ 24 , 31 ]. Regarding TaqI polymorphism, our results are in line with those obtained in previous studies of Italian subjects with periodontitis in which T (T) allele were higher in patients than in controls, although in some previous works on Caucasian population the C (t) allele seems to increase the risk of developing periodontitis.…”

“…This variant determines the creation of a new start codon at three amino acids downstream from the site of initiation of translation, with consequent alteration of the related protein. The C (F) variant therefore induces the synthesis of a shorter protein with greater biological activity and more effective in the transcriptional activity of the vitamin D signal [ 31 , 35 ]. The TT + CT+ (ff +Ff) genotypes are associated with lower bone mineral density than the CC (FF) genotype, as available on the Pharmacogenomics Knowledgebase (PharmGKB) (PharmGKB ID: 769164470) [ 54 ] and confirmed by a recent meta-analysis published this year conducted on 14 studies with 2219 participants [ 32 ].…”

“…Research on genetic factors has focused primarily on genes modulating the immune system, such as genes encoding for the cytokines IL1A, IL1B, IL10, and IL6, considered key factors in the inflammatory process during periodontal disease [ 8 , 22 , 23 ]. Numerous studies have also been performed on vitamin D receptor (VDR) encoding gene polymorphisms BsmI, TaqI, FokI, and ApaI, opening to new considerations [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Once activated, the VDR protein modulates the transcription of genes that promote the functions of vitamin D, and it is established that its sequence variants are associated with dysfunctions in the metabolism of vitamin D [ 29 , 30 ].…”

Synergic Action of Insulin-like Growth Factor-2 and miRNA-483 in Pterygium Pathogenesis

“…Among the 52 pterygium samples, 48 specimens were 10% formalin-fixed and paraffinembedded; moreover, 11 epibulbar conjunctiva specimens, belonging to a group of 15 samples from healthy donors, were formalin-fixed, processed for paraffin embedding, and used as normal controls. Three microtome histological sections (6-7 µm thick) per sample were subjected to immunohistochemistry (IHC) for the demonstration of IGF-2 and IGF-1R antigens using the streptavidin-biotin alkaline phosphatase method, as previously described [7,53]. These were dewaxed, rehydrated, and rinsed in phosphate-buffered saline (PBS), pH 7.4.…”

Vitamin D, the Vitamin D Receptor, Calcitriol Analogues and Their Link with Ocular Diseases

“…In healthy conjunctiva, VDR was localized mainly in the cytoplasm, while in pterygium cells, VDR was co-localized in the nucleus and cytoplasm. Hence, the nuclear signaling pathways related to VDR may be engaged in the pathogenesis of pterygium [ 183 ]. Further analyses and clinical trials are needed to standardize the role of VDR in pathogenesis and the development of pterygium.…”