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Xiaohua Li, Xiaohua Li, Min Yuan, Ruijie Yin; Epigenetic factors in the pathogenesis of corneal dystrophy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1582.
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Tumor suppressor gene Hypermethylated In Cancer 1( HIC1) regulates the expression of SIRT1 and in turn SIRT1 deacetylates of P53 (AC-p53) leading to the response to DNA repair, stress and senesces, therefore, a HIC1, SIRT 1 and P53 loop have been implied in the pathogenesis of cancer, ageing and degenerative diseases. The current research sought to investigate the roles of HIC1, SIRT1 and P53 in the pathogenesis of corneal dystrophy and its association with CTGF and TGF-beta expression.
Formalin-fixed paraffin embedded cornea section from 25 patients (ages 5-68; 17 male, 8 female) with corneal dystrophy were prepared for the study.Five corneal specimens from normal adult were included as control. H&E, PAS, Congo red, Masson and colloidal iron staining were performed to confirm the diagnosis of corneal dystrophy. Sections were analyzed for the expressions of HIC1, SIRT1, acetylated -P53, CTGF, TGF-beta, and α-SMA by immunohistochemistry. The red chromagen color was developed using amino ethyl carbazole. The Slides were examined using a digit microscope.
14 cases were diagnosed with macular corneal dystrophy and 11 cases were diagnosed with lattice corneal dystrophy according to H&E and histochemical staining. In cases of macular dystrophy, the deposits were positive with colloidal iron staining, while in cases of lattice dystrophy, the deposits stained positively with Masson trichrome, PAS and Congo red staining. In corneal specimen both macular corneal and lattice corneal dystrophy, HIC1 was highly expressed compared with control especially in corneal epithelial cell . The expression of SIRT1 was much weaker compared with the HIC1 and normal corneal specimens staining. Notably, Acetylated P53 immnunoreactivity is abundant in the degenerated areas of the cornea. In addition, the increased expression of fibrotic inducer such as CTGF and TGF-beta were seen in the corneal fibrosis lesion, striking, the expression of CTGF was much stronger than TGF-beta. α-SMA was also unregulated in the area where CTGF was detected.
The high HIC1 expression is associated with increased expression of Ac-p53 and CTGF and the down regulation of SIRT1 in the corneal tissue; the distinct expression of the epigenetic factors HIC1, SIRT1, AC-p53 and their interaction with CTGF may play an essential role in pathogenesis of the corneal dystrophy.
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