PDF(Pubmed)
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.
摘要：
碳酸酐酶2（Car2）基因编码负责房水（AH）产生的主要同工酶，并在调节眼内压（IOP）中起主要作用。CRISPR-Cas9系统,基于ShH10腺病毒相关病毒，可以有效地破坏睫状体中的Car2基因。一次玻璃体内注射，在正常小鼠和青光眼模型中,Car2敲除可通过抑制AH产生而显著且持续地降低IOP。此外，在慢性高眼压模型中，它有效地延迟甚至阻止由长期高眼压引起的青光眼损伤，超越临床上可用的碳酸酐酶抑制剂如布林佐胺的功效。基于CRISPR-Cas9的Car2破坏的临床应用是一种有吸引力的治疗策略，可以为青光眼患者带来额外的益处。
