[Show abstract][Hide abstract] ABSTRACT: Elevated eye pressure is the main risk factor for glaucoma, and intraocular pressure rises when the balance between aqueous humor formation and outflow resistance is compromised. In a normal eye there is a precise tune of aqueous outflow under the fine control of ciliary body and trabecular meshwork. Current pharmacological therapies for lowering the intraocular pressure in glaucoma include increasing aqueous humor outflow and suppression of aqueous humor production. However, most of antiglaucoma drugs currently on the market do not target the trabecular meshwork that represents the site of the pathology. This review focuses on pharmacological management of ocular hypertension with a particular attention to the future pharmacotherapy scenario.
Current Opinion in Pharmacology 10/2012; 13(1). DOI:10.1016/j.coph.2012.09.012 · 4.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Elevated intraocular pressure (IOP) is considered as the major risk factor for the loss of retinal ganglion cells (RGCs) and their axons in glaucoma. Emerging evidence suggests elevated IOP can induce Drp1 upregulation and mitochondrial fission, which is involved in cell death. However, the underlying mechanism for these effects remains unknown. The present study used RNAi screening to investigate the effects of 24 kinases associated with mitochondrial activities on DRP1 expression under hydrostatic pressure. We identified, for the first time, that glycogen synthase kinase 3 beta (GSK3β) knockdown suppressed the upregulation of DRP1 induced by elevated pressure. Use of the pharmacological inhibitor of GSK3β inhibitor, lithium chloride (LiCl), confirmed this result. Furthermore, we demonstrated that one of the mechanisms of lithium chloride neuroprotection might be via inhibition of mitochondrial fission through downregulation of Drp1.
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