CRISPR-CasRx-mediated disruption of Aqp1/Adrb2/Rock1/Rock2 genes reduces intraocular pressure and retinal ganglion cell damage in mice.
Mingyu YaoZhenhai ZengSiheng LiZhilin ZouZhongxing ChenXinyi ChenQingyi GaoGuoli ZhaoAodong ChenZheng LiYiran WangRui NingColm McAlindenXingtao ZhouJinhai HuangPublished in: Nature communications (2024)
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 β2 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 β2 adrenergic receptor in female mice, reduces the intraocular pressure and secures the retina ganglion cells by single-cell sequencing.
Keyphrases
- single cell
- optic nerve
- high fat diet induced
- induced apoptosis
- cell cycle arrest
- rna seq
- genome wide
- poor prognosis
- stem cells
- oxidative stress
- binding protein
- mesenchymal stem cells
- wild type
- type diabetes
- gene expression
- ionic liquid
- crispr cas
- cell proliferation
- signaling pathway
- high throughput
- bone marrow
- optical coherence tomography
- adipose tissue
- spinal cord injury
- spinal cord
- skeletal muscle
- cell death
- pi k akt