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CRISPR-Cas9-mediated deletion of carbonic anhydrase 2 in the ciliary body to treat glaucoma.
Jiang, Jiaxuan; Kong, Kangjie; Fang, Xiuli; Wang, Deming; Zhang, Yinhang; Wang, Peiyuan; Yang, Zefeng; Zhang, Yuwei; Liu, Xiaoyi; Aung, Tin; Li, Fei; Yu-Wai-Man, Patrick; Zhang, Xiulan.
Afiliação
  • Jiang J; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Disease, Guangzhou 510060, China.
  • Kong K; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Disease, Guangzhou 510060, China.
  • Fang X; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Disease, Guangzhou 510060, China.
  • Wang D; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Disease, Guangzhou 510060, China.
  • Zhang Y; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Disease, Guangzhou 510060, China.
  • Wang P; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Disease, Guangzhou 510060, China.
  • Yang Z; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Disease, Guangzhou 510060, China.
  • Zhang Y; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Disease, Guangzhou 510060, China.
  • Liu X; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Disease, Guangzhou 510060, China.
  • Aung T; Singapore Eye Research Institute and Singapore National Eye Centre, Singapore, Singapore; National University of Singapore, Singapore, Singapore.
  • Li F; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Disease, Guangzhou 510060, China. Electronic address: lifei.aletheus@gmail.com
  • Yu-Wai-Man P; Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; MRC Mitochondrial Biology Unit, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; Cambridge Eye Unit, Addenbrooke's Hospital, Cambridge University Hospitals, C
  • Zhang X; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Disease, Guangzhou 510060, China. Electronic address: zhangxl2@mail.sysu.edu.c
Cell Rep Med ; 5(5): 101524, 2024 May 21.
Article em En | MEDLINE | ID: mdl-38670096
ABSTRACT
The carbonic anhydrase 2 (Car2) gene encodes the primary isoenzyme responsible for aqueous humor (AH) production and plays a major role in the regulation of intraocular pressure (IOP). The CRISPR-Cas9 system, based on the ShH10 adenovirus-associated virus, can efficiently disrupt the Car2 gene in the ciliary body. With a single intravitreal injection, Car2 knockout can significantly and sustainably reduce IOP in both normal mice and glaucoma models by inhibiting AH production. Furthermore, it effectively delays and even halts glaucomatous damage induced by prolonged high IOP in a chronic ocular hypertension model, surpassing the efficacy of clinically available carbonic anhydrase inhibitors such as brinzolamide. The clinical application of CRISPR-Cas9 based disruption of Car2 is an attractive therapeutic strategy that could bring additional benefits to patients with glaucoma.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glaucoma / Corpo Ciliar / Anidrase Carbônica II / Sistemas CRISPR-Cas / Pressão Intraocular Limite: Animals / Humans Idioma: En Revista: Cell Rep Med Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glaucoma / Corpo Ciliar / Anidrase Carbônica II / Sistemas CRISPR-Cas / Pressão Intraocular Limite: Animals / Humans Idioma: En Revista: Cell Rep Med Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos