Int J Med Sci 2020; 17(8):1062-1070. doi:10.7150/ijms.43614 This issue

Research Paper

Cross-talk between MYOC p. Y437H mutation and TGF-β2 in the pathology of glaucoma

Yang Yang1,2, AL Sabri Waled Abdulghani Abdulatef1, LuSi Zhang3, Haibo Jiang1, Zhou Zeng1, Haibo Li1,4✉, Xiaobo Xia1,4✉

1. Eye center of Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
2. Department of Ophthalmology, the First People's Hospital of Yueyang, Yueyang, 414000, Hunan Province, China
3. The School of Life Sciences, Central South University, Changsha 410078, Hunan Province, China
4. Hunan Key Laboratory of Ophthalmology, Central South University, Changsha 410008, Hunan Province, China

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Yang Y, Abdulatef ALSWA, Zhang L, Jiang H, Zeng Z, Li H, Xia X. Cross-talk between MYOC p. Y437H mutation and TGF-β2 in the pathology of glaucoma. Int J Med Sci 2020; 17(8):1062-1070. doi:10.7150/ijms.43614. Available from

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Objective: To identify the interaction between the MYOC Y437H mutation and TGF-β2 in a family with primary open-angle glaucoma (POAG).

Methods: The MYOC Y437H mutation was identified in a family with POAG; the family was a fourth-generation family with 27 members, of which 6 members were affected. Analysis focused on the secreted myocilin protein and TGF-β2 found in the aqueous humor. Samples were taken both from normal controls and MYOC mutant carriers and cross-talk between MYOC Y437H and TGF-β2 were evaluated in the trabecular meshwork (TM) cells.

Results: Aqueous humor secreted myocilin protein levels were reduced while TGF-β2 levels were increased in patients with the MYOC (c.1309T>C) mutation. This inverse relationship indicated that elevated TGF-β2 may be an important pathogenic mechanism in the progression of myocilin-related POAG. In TM cells expressing the MYOC Y437H mutant, exogenous TGF-β2 also significantly increased myocilin expression as well as the endoplasmic reticulum (ER) stress markers GRP94 and CHOP. This increase in TGF-β2 was also associated with increased cell death in cells carrying the MYOC Y437H mutation.

Conclusion: These data collectively suggest that the mutual interaction between glaucomatous MYOC mutation and TGF-β2 contributed to the cell death of TM cells. This relationship also provides a new, therapeutic targets for the treatment of glaucoma.

Keywords: Glaucoma, MYOC, Aqueous humor, TGF-β2