Innovative Vision Products, Inc., County of New Castle, DE 19810, USA.
Curr Mol Med. 2011 Oct;11(7):528-52. doi: 10.2174/156652411800615126.
Glaucoma is a major cause of irreversible blindness, affecting more than 70 million individuals worldwide. Elevated intraocular pressure (IOP) is a major risk factor in the development of glaucoma and in the progression of glaucomatous damage. High IOP usually occurs as a result of an increase in aqueous humor outflow resistance in trabecular meshwork (TM). Primary open angle glaucoma (POAG) is characterized by quantifiable parameters including the IOP, the aqueous outflow facility, and geometric measurements of the optic disc and visual defects. Morphological and biochemical analyses of the TM of POAG patients revealed loss of cells, increased accumulation of extracellular matrix (ECM), changes in the cytoskeleton, cellular senescence and the process of subclinical inflammation. Various biochemical and molecular biology biomarkers of TM cells senescence are considered in the article. Oxidative stress is becoming an important factor more likely to be involved in the pathogenesis of POAG. Treatment of TM cells with oxidative stress induced POAG-typical changes like ECM accumulation, cell death, disarrangement of the cytoskeleton, advanced senescence and the release of inflammatory markers. Oxidative stress is able to induce characteristic glaucomatous TM changes and these oxidative stress-induced TM changes can be minimized by the use of antioxidants, such as carnosine-related analogues and IOP-lowering substances. There is evidence demonstrating that carnosine related analogues may have antioxidative capacities, can prevent cellular senescence and the attrition of telomeres during the action of oxidative stress. Prevention of oxidative stress exposure to the TM with N-acetylcarnosine ophthalmic prodrug of carnosine and oral formulation of non-hydrolized carnosine may help to reduce the progression of POAG. The previous work has demonstrated that carnosine is able to reach the TM directly via the transcorneal and systemic pathways of administration with N-acetylcarnosine ophthalmic prodrug and oral formulation of non-hydrolized carnosine. We suggest in this article that dual therapy with N-acetylcarnosine lubricant eye drops, oral formulation of non-hydrolized carnosine combined with anti-glaucoma adrenergic drug may become the first-line therapy in glaucoma due to their efficiency in reducing IOP, prevention and reversal of oxidative stress-induced damages in TM and the low rate of severe side effects during combined treatment.
青光眼是一种主要的不可逆失明原因，影响全球超过 7000 万人。眼内压升高（IOP）是青光眼发展和青光眼损害进展的主要危险因素。IOP 升高通常是由于小梁网（TM）中的房水流出阻力增加所致。原发性开角型青光眼（POAG）的特征是可量化的参数，包括 IOP、房水流出率以及视盘和视觉缺陷的几何测量。POAG 患者 TM 的形态和生化分析显示细胞丢失、细胞外基质（ECM）积累增加、细胞骨架变化、细胞衰老和亚临床炎症过程。本文考虑了 TM 细胞衰老的各种生化和分子生物学生物标志物。氧化应激正在成为一种重要的因素，更可能参与 POAG 的发病机制。用氧化应激处理 TM 细胞会导致 ECM 积累、细胞死亡、细胞骨架排列紊乱、衰老加速和炎症标志物释放等 POAG 典型变化。氧化应激能够诱导特征性的青光眼 TM 变化，这些氧化应激诱导的 TM 变化可以通过使用抗氧化剂如肌肽相关类似物和降低 IOP 的物质来最小化。有证据表明，肌肽相关类似物可能具有抗氧化能力，可以在氧化应激作用下防止细胞衰老和端粒磨损。用 N-乙酰肌肽眼科前药和非水解肌肽的口服制剂预防 TM 暴露于氧化应激可能有助于减缓 POAG 的进展。以前的工作已经证明，N-乙酰肌肽眼科前药和非水解肌肽的口服制剂可以通过角膜和全身途径直接到达 TM。我们在本文中建议，N-乙酰肌肽润滑滴眼液与非水解肌肽的口服制剂联合使用，加上抗青光眼肾上腺素能药物的双重治疗可能成为青光眼的一线治疗方法，因为它们在降低 IOP、预防和逆转 TM 中氧化应激诱导的损伤以及在联合治疗期间严重副作用发生率低方面具有效率。
