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• According to present study, a novel approach to investigation of the pathogenesis of pterygium has been created in an immunological field.
• This is the firsthand attempt to inspect the association of epigenetic changes of the CTLA4 gene and pathogenesis of pterygia.
• We believe that increase of CTLA4 gene expression can be a trigger which promote pterygium enlargement, dependent on a negative self-regulation of T cells.
• We have submitted a credible evidence of CTLA4 gene expression in human eye tissue.
BackgroundPterygium is the human eye lesion whose prevalence in the general population is estimated about 2%. The disease, in extreme phase, can lead to visual disturbance and eventually causes complete loss of vision due to the lesion growth over the papillary axis. Pterygium invasive tissue is a tumor-like tissue that is initially identified and then is attacked by cytotoxic T cells. Cytotoxic T lymphocyte associated antigen 4 (CTLA4), as a modulator molecule of the adaptive immune system, plays a critical role in maintaining peripheral T cell tolerance by diminishing its responsiveness and increasing its activation threshold. The aim of this study is to investigate the association between some epigenetic changes of the CTLA4 gene, such as promoter methylation and gene expression, and pathogenesis of pterygia.Materials and methodsGenomic DNA was extracted from 75 formalin-fixed, paraffin-embedded tissues of pterygia and 70 specimens of normal conjunctiva from eyes without pterygium as the control group, collected from Sistan and Baluchestan population. CTLA4 gene promoter methylation was carried out by methylation-specific PCR technique. The gene expression analysis was done on extracted total RNA from 20 healthy and 23 pterygium tissue samples using Real-Time PCR technique.ResultsPromoter methylation changes of CTLA4 gene were not statistically different in patients with pterygium in comparison with healthy controls (OR = 1.614; 95% CI = 0.57–4.75; P value = 0.37). However, gene expression level of CTLA4 was remarkably different in patients and healthy controls (Mean ± SD: 1.343 ± 0.133 and 2.027 ± 0.219, respectively; P value = 0.009).ConclusionThis is a credible evidence of CTLA4 gene expression in human eye tissue. This first hand attempt of investigating the association of epigenetic changes of the CTLA4 gene and pathogenesis of pterygia, indicated a significant intensification of the gene expression of CTLA4 in patients with pterygia. We suggest that increasing CTLA4 gene expression can be a trigger which promotes pterygium enlargement. However, further studies on more populations with larger sample sizes need to be done to verify this hypothesis in the future.
Journal: Gene - Volume 583, Issue 2, 1 June 2016, Pages 130–133