Chatterjee Ayan, Villarreal Guadalupe, Rhee Douglas J
Department of Ophthalmology and Visual Sciences, University Hospitals Eye Institute, Case Western Reserve University School of Medicine , Cleveland, Ohio.
J Ocul Pharmacol Ther. 2014 Aug;30(6):447-63. doi: 10.1089/jop.2014.0013. Epub 2014 Jun 5.
Abstract Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, and intraocular pressure (IOP) is an important modifiable risk factor. IOP is a function of aqueous humor production and aqueous humor outflow, and it is thought that prolonged IOP elevation leads to optic nerve damage over time. Within the trabecular meshwork (TM), the eye's primary drainage system for aqueous humor, matricellular proteins generally allow cells to modulate their attachments with and alter the characteristics of their surrounding extracellular matrix (ECM). It is now well established that ECM turnover in the TM affects outflow facility, and matricellular proteins are emerging as significant players in IOP regulation. The formalized study of matricellular proteins in TM has gained increased attention. Secreted protein acidic and rich in cysteine (SPARC), myocilin, connective tissue growth factor (CTGF), and thrombospondin-1 and -2 (TSP-1 and -2) have been localized to the TM, and a growing body of evidence suggests that these matricellular proteins play an important role in IOP regulation and possibly the pathophysiology of POAG. As evidence continues to emerge, these proteins are now seen as potential therapeutic targets. Further study is warranted to assess their utility in treating glaucoma in humans.
摘要 原发性开角型青光眼(POAG)是全球失明的主要原因,而眼压(IOP)是一个重要的可调节风险因素。眼压是房水生成和房水流出的函数,长期眼压升高被认为会随着时间的推移导致视神经损伤。在小梁网(TM)中,眼睛房水的主要引流系统,基质细胞蛋白通常允许细胞调节它们与周围细胞外基质(ECM)的附着并改变其特性。现在已经明确,小梁网中的细胞外基质周转会影响房水流出率,并且基质细胞蛋白正在成为眼压调节中的重要参与者。对小梁网中基质细胞蛋白的正式研究越来越受到关注。富含半胱氨酸的酸性分泌蛋白(SPARC)、肌纤蛋白、结缔组织生长因子(CTGF)以及血小板反应蛋白-1和-2(TSP-1和TSP-2)已定位到小梁网,越来越多的证据表明这些基质细胞蛋白在眼压调节以及可能在原发性开角型青光眼的病理生理学中起重要作用。随着证据不断出现,这些蛋白现在被视为潜在的治疗靶点。有必要进一步研究以评估它们在治疗人类青光眼方面的效用。