机构:[1]Department of Ophthalmology and Ophthalmic Laboratories, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.四川大学华西医院[2]Schepens Eye Research Institute, Massachusetts Eye & Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.[3]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 54 South Xianlie Road, Guangzhou, Guangdong, P. R. China.[4]Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, Comprehensive Cancer Center, Department of Pathology, University of Michigan Ann Arbor, Michigan, USA.[5]Division of Ophthalmology, Surgical Service, Veterans Administration Ann Arbor Healthcare System, Ann Arbor, Michigan, USA. 6Veterans Administration Boston Healthcare System, Boston, Massachusetts, USA
Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ∼50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT) Ezh2 from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of Six1 and its targets. Forced expression of Six1 in the postnatal retina was sufficient to induce photoreceptor degeneration. Ezh2, although enriched in the embryonic retina, was not present in the mature retina; these data reveal an Ezh2-mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy.
基金:
This research was supported by funding from the Department of Veterans Affairs (1I01RX000110), NIH/NEI
(R41 EY025913 and R01EY025259) and Curing Kids Fund to D.F.C.; the Core Grant for Vision Research from
NIH/NEI to the Schepens Eye Research Institute (P30EY03790); the National Natural Science Foundation of
China (81371024) and Science and Technology Department of Sichuan Province (2014SZ0030) to N.H.Y.; and
National Institutes of Health (K12EY022299) and Research to Prevent Blindness to R.C.R.
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2016]版:
大类|2 区综合性期刊
小类|2 区综合性期刊
最新[2023]版:
大类|2 区综合性期刊
小类|2 区综合性期刊
第一作者:
第一作者机构:[1]Department of Ophthalmology and Ophthalmic Laboratories, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.[2]Schepens Eye Research Institute, Massachusetts Eye & Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
通讯作者:
通讯机构:[2]Schepens Eye Research Institute, Massachusetts Eye & Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.[4]Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, Comprehensive Cancer Center, Department of Pathology, University of Michigan Ann Arbor, Michigan, USA.[5]Division of Ophthalmology, Surgical Service, Veterans Administration Ann Arbor Healthcare System, Ann Arbor, Michigan, USA. 6Veterans Administration Boston Healthcare System, Boston, Massachusetts, USA
推荐引用方式(GB/T 7714):
Yan Naihong,Cheng Lin,Cho Kinsang,et al.Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1.[J].Scientific reports.2016,6:33887.doi:10.1038/srep33887.
APA:
Yan Naihong,Cheng Lin,Cho Kinsang,Malik Muhammad Taimur A,Xiao Lirong...&Chen Dong Feng.(2016).Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1..Scientific reports,6,
MLA:
Yan Naihong,et al."Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1.".Scientific reports 6.(2016):33887