RT Journal Article
SR Electronic
T1 Optogenetic stimulation of phosphoinositides reveals a critical role of primary cilia in eye pressure regulation
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaay8699
DO 10.1126/sciadv.aay8699
VO 6
IS 18
A1 Prosseda, Philipp P.
A1 Alvarado, Jorge A.
A1 Wang, Biao
A1 Kowal, Tia J.
A1 Ning, Ke
A1 Stamer, W. Daniel
A1 Hu, Yang
A1 Sun, Yang
YR 2020
UL http://advances.sciencemag.org/content/6/18/eaay8699.abstract
AB 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 IFT88fl/fl 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.