Involvement of Endothelin-1 in the Pathophysiology of Normal-Tension Glaucoma

Tetsuya Sugiyama


In this review, the involvement of endothelin (ET)-1 in the pathophysiology of normal-tension glaucoma (NTG) is summarized. Several ETs were first isolated in Japan in 1988, and were identified as some of the most potent vasoconstrictors. The roles of ETs in the eyes and ocular diseases have been investigated worldwide. ET-1 is a potential participant in the local regulation of several fundamental processes, including intraocular pressure (IOP), ocular blood flow, axonal transport, and neural degeneration. Of these, the effects on IOP are not addressed in this review, and we instead focus on the pathophysiology of NTG. Several studies have reported abnormal plasma ET-1 levels or their response to postural changes in NTG. As a chronic ischemic optic nerve head model induced by ET-1 injections produces retinal ganglion cell-specific cell death and many cellular changes similar to glaucoma, many studies have been conducted on neuroprotection for glaucomatous optic neuropathy using this animal model. Genetic studies on ET receptors have provided evidence that polymorphisms of ETA andETB receptors may be associated with increased NTG risk. In vitro studies have suggested that ET-1 may cause the death of retinal neurons through glutamate and nitric oxide synthase. ET-1 further affects the functions of glial and lamina cribrosa (LC) cells, and may contribute to remodeling of the extracellular matrix at the LC level in glaucoma. Although few studies have yet obtained promising results showing that ET receptor antagonists can be clinically useful for NTG, blockade of ET receptors is a potentially attractive target for treating this critical ocular disease.

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