ATP sensitive potassium channel openers: A new class of ocular hypotensive agents

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Abstract

ATP sensitive potassium (KATP) channels connect the metabolic and energetic state of cells due to their sensitivity to ATP and ADP concentrations. KATP channels have been identified in multiple tissues and organs of the body including heart, pancreas, vascular smooth muscles and skeletal muscles. These channels are obligatory hetero-octamers and contain four sulfonylurea (SUR) and four potassium inward rectifier (Kir) subunits. Based on the particular type of SUR and Kir present, there are several tissue specific subtypes of KATP channels, each with their own unique set of functions. Recently, KATP channels have been reported in human and mouse ocular tissues. In ex vivo and in vivo model systems, KATP channel openers showed significant ocular hypotensive properties with no appearance of toxic side effects. Additionally, when used in conjunction with known intraocular pressure lowering drugs, an additive effect on IOP reduction was observed. These KATP channel openers have also been reported to protect the retinal ganglion cells during ischemic stress and glutamate induced toxicity suggesting a neuroprotective property for this drug class. Medications that are currently used for treating ocular hypertensive diseases like glaucoma do not directly protect the affected retinal cells, are sometimes ineffective and may show significant side effects. In light of this, KATP channel openers with both ocular hypotensive and neuroprotective properties, have the potential to develop into a new class of glaucoma therapeutics.

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