Optogenetic stimulation of phosphoinositides reveals a critical role of primary cilia in eye pressure regulation.

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^fl/fl mice that lack functional cilia. Thus, our st

SUBMITTER: Prosseda PP 

PROVIDER: S-EPMC7190330 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature