CRISPR-CasRx-mediated disruption of Aqp1/Adrb2/Rock1/Rock2 genes reduces intraocular pressure and retinal ganglion cell damage in mice.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39080269.
- Also identified by DOI 10.1038/s41467-024-50050-4 and PMC identifier 11289368.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Retinal Ganglion Cells
- rho-Associated Kinases
- Intraocular Pressure
- Aquaporin 1
- Glaucoma
- CRISPR-Cas Systems