Optogenetic stimulation of phosphoinositides reveals a critical role of primary cilia in eye pressure regulation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32494665.
- Also identified by DOI 10.1126/sciadv.aay8699 and PMC identifier 7190330.
- Licence recorded as CC BY-NC.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Glaucoma is a group of progressive optic neuropathies that cause irreversible vision loss. Although elevated intraocular pressure (IOP) is associated with the development and progression of glaucoma, the mechanisms for its regulation are not well understood. Here, we have designed CIBN/CRY2-based optogenetic constructs to study phosphoinositide regulation within distinct subcellular compartments. We show that stimulation of CRY2-OCRL, an inositol 5-phosphatase, increases aqueous humor outflow and lowers IOP in vivo, which is caused by a calcium-dependent actin rearrangement of the trabecular meshwork cells. Phosphoinositide stimulation also rescues defective aqueous outflow and IOP in a Lowe syndrome mouse model but not in IFT88<sup>fl/fl</sup> mice that lack functional cilia. Thus, our study is the first to use optogenetics to regulate eye pressure and demonstrate that tight regulation of phosphoinositides is critical for aqueous humor homeostasis in both normal and diseased eyes.