CRISPR-CasRx-mediated disruption of Aqp1/Adrb2/Rock1/Rock2 genes reduces intraocular pressure and retinal ganglion cell damage in mice

被引：5

作者：

Yao, Mingyu ^{[1
,2
,3
,4
,5
]}

Zeng, Zhenhai ^{[1
,2
,3
,4
,5
]}

Li, Siheng ^{[1
,2
,3
,4
,6
]}

Zou, Zhilin ^{[6
]}

Chen, Zhongxing ^{[1
,2
,3
,4
,5
]}

Chen, Xinyi ^{[6
]}

Gao, Qingyi ^{[1
,2
,3
,4
,5
]}

Zhao, Guoli ^{[1
,2
,3
,4
,5
]}

Chen, Aodong ^{[6
]}

Li, Zheng ^{[6
]}

Wang, Yiran ^{[1
,2
,3
,4
,5
]}

Ning, Rui ^{[1
,2
,3
,4
,5
]}

McAlinden, Colm ^{[1
,2
,3
,4
,7
,8
]}

Zhou, Xingtao ^{[1
,2
,3
,4
,5
]}

Huang, Jinhai ^{[1
,2
,3
,4
,5
]}

机构：

[1] Fudan Univ, Eye & ENT Hosp, Eye Inst, Shanghai, Peoples R China

[2] Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, Shanghai, Peoples R China

[3] Chinese Acad Med Sci, NHC Key Lab Myopia & Related Eye Dis, Shanghai, Peoples R China

[4] Chinese Acad Med Sci, Key Lab Myopia & Related Eye Dis, Shanghai, Peoples R China

[5] Shanghai Res Ctr Ophthalmol & Optometry, Shanghai, Peoples R China

[6] Wenzhou Med Univ, Eye Hosp, Sch Ophthalmol & Optometry, Wenzhou, Zhejiang, Peoples R China

[7] Queen Victoria Hosp, Corneo Plast Unit, E Grinstead, England

[8] Queen Victoria Hosp, Eye Bank, E Grinstead, England

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

基金：

中国国家自然科学基金;

关键词：

CYCLIC MECHANICAL-STRESS; TRABECULAR MESHWORK; OCULAR HYPERTENSION; EPITHELIAL-CELLS; GLAUCOMA; EXPRESSION; PROGRESSION; PREVALENCE; INHIBITION; BLINDNESS;

D O I：

10.1038/s41467-024-50050-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Glaucoma affects approximately 80 million individuals worldwide, a condition for which current treatment options are inadequate. The primary risk factor for glaucoma is elevated intraocular pressure. Intraocular pressure is determined by the balance between the secretion and outflow of aqueous humor. Here we show that using the RNA interference tool CasRx based on shH10 adenovirus-associated virus can reduce the expression of the aqueous humor circulation related genes Rock1 and Rock2, as well as aquaporin 1 and beta 2 adrenergic receptor in female mice. This significantly reduced intraocular pressure in female mice and provided protection to the retina ganglion cells, ultimately delaying disease progression. In addition, we elucidated the mechanisms by which the knockdown of Rock1 and Rock2, or aquaporin 1 and beta 2 adrenergic receptor in female mice, reduces the intraocular pressure and secures the retina ganglion cells by single-cell sequencing.

引用

页数：15

共 81 条

[1] RNA targeting with CRISPR-Cas13 [J].

Abudayyeh, Omar O. ;

Gootenberg, Jonathan S. ;

Essletzbichler, Patrick ;

Han, Shuo ;

Joung, Julia ;

Belanto, Joseph J. ;

Verdine, Vanessa ;

Cox, David B. T. ;

Kellner, Max J. ;

Regev, Aviv ;

Lander, Eric S. ;

Voytas, Daniel F. ;

Ting, Alice Y. ;

Zhang, Feng .

NATURE, 2017, 550 (7675) :280-+

[2] Intraocular Pressure Homeostasis: Maintaining Balance in a High-Pressure Environment [J].

Acott, Ted S. ;

Kelley, Mary J. ;

Keller, Kate E. ;

Vranka, Janice A. ;

Abu-Hassan, Diala W. ;

Li, Xinbo ;

Aga, Mini ;

Bradley, John M. .

JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS, 2014, 30 (2-3) :94-101

[3] Role of aquaporin-1 in trabecular meshwork cell homeostasis during mechanical strain [J].

Baetz, N. W. ;

Hoffman, E. A. ;

Yool, A. J. ;

Stamer, W. D. .

EXPERIMENTAL EYE RESEARCH, 2009, 89 (01) :95-100

[4]

Bakalash S, 2002, INVEST OPHTH VIS SCI, V43, P2648

[5] Immunomodulation as a Neuroprotective Strategy for Glaucoma Treatment [J].

Baris, Mine ;

Tezel, Gulgun .

CURRENT OPHTHALMOLOGY REPORTS, 2019, 7 (02) :160-169

[6] Review of rodent hypertensive glaucoma models [J].

Biswas, Sayantan ;

Wan, Kelvin H. .

ACTA OPHTHALMOLOGICA, 2019, 97 (03) :E331-E340

[7]

Borrás T, 2002, INVEST OPHTH VIS SCI, V43, P33

[8]

Bradley JMB, 2001, INVEST OPHTH VIS SCI, V42, P1505

[9] Isolation and Molecular Profiling of Primary Mouse Retinal Ganglion Cells: Comparison of Phenotypes from Healthy and Glaucomatous Retinas [J].

Chintalapudi, Sumana R. ;

Djenderedjian, Levon ;

Stiemke, Andrew B. ;

Steinle, Jena J. ;

Jablonski, Monica M. ;

Morales-Tirado, Vanessa M. .

FRONTIERS IN AGING NEUROSCIENCE, 2016, 8

[10] The role of steroids in outflow resistance [J].

Clark, Abbot F. ;

Wordinger, Robert J. .

EXPERIMENTAL EYE RESEARCH, 2009, 88 (04) :752-759

← 1 2 3 4 5 6 7 8 9 →