CHST6 mutation screening and endoplasmatic reticulum stress in macular corneal dystrophy
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Liyuan Wang1, Xianling Tang1, Xiaolin Lv1, Encheng Sun3, Donglai Wu3, Changlin Wang2 and Ping Liu1
1Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
2Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
3State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
Ping Liu, email: firstname.lastname@example.org
Keywords: CHST6; macular corneal dystrophy; endoplasmic reticulum stress; apoptosis; keratocytes
Received: August 24, 2017 Accepted: September 20, 2017 Published: October 24, 2017
Macular corneal dystrophy (MCD) is an autosomal recessive disorder mainly caused by gene mutations of carbohydrate sulfotransferase (CHST6) leading to bilateral visual impairment. Because the mechanism underlying this degeneration remains poorly understood, we investigated molecular alterations and pathways that may be involved in MCD in this issue. Different mutation sites were screened by direct sequencing of the coding region of CHST6. In addition, we described morphological changes in MCD keratocytes by light microscopy and electron microscopy and determined the relationship between the development of this disease and the occurrence of apoptosis through flow cytometry, cell counting kit-8, colony formation assay and other experiments. Western blotting and quantitative real-time polymerase chain reaction were used to determine if endoplasmic reticulum (ER) stress was activated. We found 10 kinds of mutations among these families with 3 novel mutations included. The percentage of apoptotic keratocytes increased in MCD patients; furthermore, the expression of apoptosis related protein B-cell lymphoma-2 (Bcl-2) was down-regulated while Bcl-2 associated X protein was upregulated. Finally, ER stress was activated with the upregulation of glucose-regulated protein 78 and CCAAT-enhancer-binding protein homologous protein. Our clinical and in vitro results suggest that the CHST6 mutation associated with MCD is associated with apoptosis, and ER stress is probably involved in this apoptosis pathway.
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