Bhattacharya Sanjoy K, Peachey Neal S, Crabb John W
Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Vis Neurosci. 2005 Sep-Oct;22(5):605-13. doi: 10.1017/S0952523805225099.
Primary open angle glaucoma (POAG) is a leading cause of late onset, progressive, irreversible blindness and, although its etiology is poorly understood, elevated intraocular pressure (IOP) often appears to be a contributory factor. Proteomic and Western analyses of trabecular meshwork (TM) from patients with POAG and age-matched controls originally implicated cochlin as possibly contributing to glaucoma pathogenesis. Cochlin deposits were subsequently detected in glaucomatous but not in control TM and older glaucomatous TM was found to contain higher levels of cochlin and significantly lower amounts of collagen type II. More recently, similar results were reported in DBA/2J mice, which at older ages develop elevated IOP, retinal ganglion cell degeneration, and optic nerve damage. Notably, cochlin was absent in TM from C57BL/6J, CD1, and BALBc/ByJ mice, which do not exhibit elevated IOP or glaucoma. Cochlin was found in the TM of very young DBA/2J mice, prior to elevated IOP, suggesting that over time the protein may contribute to the events leading to increased IOP and optic nerve damage. Here we review these findings and describe how future studies in DBA/2J mice can help resolve whether cochlin plays a causal role in mechanisms of POAG and elevated IOP.
原发性开角型青光眼（POAG）是导致迟发性、进行性、不可逆失明的主要原因，尽管其病因尚不清楚，但眼压升高（IOP）通常似乎是一个促成因素。对POAG患者和年龄匹配的对照组的小梁网（TM）进行蛋白质组学和蛋白质免疫印迹分析最初表明，耳蜗素可能与青光眼发病机制有关。随后在青光眼患者的TM中检测到耳蜗素沉积，而对照组TM中未检测到，并且发现老年青光眼患者的TM中耳蜗素水平较高，而II型胶原蛋白含量显著较低。最近，在DBA/2J小鼠中也报道了类似的结果，这些小鼠在老年时会出现眼压升高、视网膜神经节细胞变性和视神经损伤。值得注意的是，在C57BL/6J、CD1和BALBc/ByJ小鼠的TM中未发现耳蜗素，这些小鼠未表现出眼压升高或青光眼。在眼压升高之前的非常年轻的DBA/2J小鼠的TM中发现了耳蜗素，这表明随着时间的推移，该蛋白可能会导致眼压升高和视神经损伤。在这里，我们回顾这些发现，并描述未来在DBA/2J小鼠中的研究如何有助于确定耳蜗素在POAG和眼压升高机制中是否起因果作用。
