Optogenetic Modulation of Intraocular Pressure in a Glucocorticoid-Induced Ocular Hypertension Mouse Model.
Optogenetic Modulation of Intraocular Pressure in a Glucocorticoid-Induced Ocular Hypertension Mouse Model.
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DOI：
10.1167/tvst.10.6.10
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发表时间：
2021-05-03
影响因子：
3
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Kowal TJ;Prosseda PP;Ning K;Wang B;Alvarado J;Sendayen BE;Jabbehdari S;Stamer WD;Hu Y;Sun Y
Steroid-induced glaucoma is a common form of secondary open angle glaucoma characterized by ocular hypertension (elevated intraocular pressure [IOP]) in response to prolonged glucocorticoid exposure. Elevated IOP occurs with increased outflow resistance and altered trabecular meshwork (TM) function. Recently, we used an optogenetic approach in TM to regulate the 5-phosphatase, OCRL, which contributes to regulating PI(4,5)P2 levels. Here, we applied this system with the aim of reversing compromised outflow function in a steroid-induced ocular hypertension mouse model. Elevated IOP was induced by chronic subconjunctival dexamethasone injections in wild-type C57Bl/6j mice. AAV2 viruses containing optogenetic modules of cryptochrome 2 (Cry2)-OCRL-5ptase and CIBN-GFP were injected into the anterior chamber. Four weeks after viral expression and dexamethasone exposure, IOP was measured by tonometer and outflow facility was measured by perfusion apparatus. Human TM cells were treated with dexamethasone, stimulated by light and treated with rhodamine-phalloidin to analyze actin structure. Dexamethasone treatment elevated IOP and decreased outflow facility in wild-type mice. Optogenetic constructs were expressed in the TM of mouse eyes. Light stimulation caused CRY2-OCRL-5ptase to translocate to plasma membrane (CIBN-CAAX-GFP) and cilia (CIBN-SSTR3-GFP) in TM cells, which rescued the IOP and outflow facility. In addition, aberrant actin structures formed by dexamethasone treatment were reduced by optogenetic stimulation in human TM cells in culture. Subcellular targeting of inositol phosphatases to remove PIP2 represents a promising strategy to reverse defective TM function in steroid-induced ocular hypertension. Targeted modulation of OCRL may be used to decrease steroid-induced elevated IOP.
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影响因子：
4.4
作者：
Filla MS;Schwinn MK;Sheibani N;Kaufman PL;Peters DM
通讯作者：
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2.3
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影响因子：
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通讯作者：
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