Institute of Clinical Physiology, Charité, Campus Benjamin Franklin, Freie Universität and Humboldt-Universität Berlin, Berlin, Germany.
Br J Pharmacol. 2011 Feb;162(4):806-16. doi: 10.1111/j.1476-5381.2010.01103.x.
Endothelin, the most potent vasoactive peptide known to date, has been suggested to play a potential role in the pathogenesis of open-angle glaucoma. Open-angle glaucoma is the most common optic nerve head neuropathy and is associated with a loss of retinal ganglion cells and visual field damage. Although an increased intraocular pressure is a major risk factor for glaucomatous optic neuropathy, other factors such as a reduced ocular blood flow play an important role for appearance of the disease. Thus, treatment of glaucoma is focused on lowering of intraocular pressure and preventing the occurrence or progression of glaucomatous optic neuropathy. Endothelin participates in the regulation of intraocular pressure by an effect on trabecular outflow, the main route for aqueous humour outflow from the eye. Trabecular outflow is modulated by trabecular meshwork contractility which is affected by endothelin. In addition to the effects of endothelin in the anterior part of the eye, the vasoconstrictor causes a decrease in ocular blood flow followed by pathological changes in the retina and the optic nerve head which is assumed to contribute to the degeneration of retinal ganglion cells. In sum, inhibition of endothelin signalling leads to lowering of intraocular pressure and exerts neuroprotective effects. Thus, endothelin antagonism in the eye represents a promising approach for pharmacological treatment of glaucoma.
内皮素是目前已知的最有效的血管活性肽，它被认为在开角型青光眼的发病机制中起潜在作用。开角型青光眼是最常见的视神经头部神经病变，与视网膜神经节细胞的丧失和视野损伤有关。虽然眼内压升高是青光眼视神经病变的主要危险因素，但其他因素，如眼血流减少，对疾病的发生也起着重要作用。因此，青光眼的治疗主要集中在降低眼内压和预防青光眼视神经病变的发生或进展。内皮素通过对小梁流出的影响参与眼压的调节，小梁流出是眼内液从眼睛流出的主要途径。小梁流出受小梁网收缩性的调节，而内皮素会影响小梁网收缩性。除了内皮素在前眼部的作用外，血管收缩剂还会导致眼血流减少，随后视网膜和视神经头部发生病理变化，这被认为是导致视网膜神经节细胞变性的原因。总之，抑制内皮素信号传导会导致眼内压降低，并发挥神经保护作用。因此，眼部内皮素拮抗作用代表了治疗青光眼的一种有前途的药理学方法。
