Clinical and cell biological investigations into mechanisms of glaucoma induced optic nerve cell death.

临床研究综述：应用激光扫描偏振仪对60名正常人120只眼的视网膜神经纤维层厚度进行了测量。测量视盘直径为1.75 mm的乳头环和距视盘边缘0.8 mm的乳头环。两环的RNFLT与年龄无显著相关性。但随着年龄的增长，总鼻腔面积的RNFLT比值显著降低。双眼RNFLT差值随年龄增长而增大。用猴眼进行的神经生物学实验表明，青光眼患者视神经头中转化生长因子-β的表达高于正常眼。这可能与青光眼视盘拔罐的进展有关。与正常眼相比，青光眼猴眼神经营养因子、NGF、BDNF和CNRF的表达降低，而Trk B和CNTFR的表达增加。神经营养因子可能与青光眼所致视神经损伤有关。此外，在大鼠实验性青光眼模型中，在肿胀的轴突中观察到外膜破坏的变性线粒体，以及视网膜神经纤维层中caspase3的高表达，这表明细胞色素c可能释放到胞浆中，这是已知的凋亡级联反应的关键开关。

The summary of the clinical study : Using a scanning laser polarimeter, we measured the thickness of retinal nerve fiber layer (RNFLT) in 120 eyes of 60 normal subjects. Measurements were made along the peripapillary ring with the diameter of 1.75 disc diameter and another one 0.8 mm away from the disc margin. The RNFLT was not significantly correlated with age along the two rings. However, the RNFLT ratio of total/nasal area significantly decreased with increase in age. There was an increase in the difference of RNFLT between both eyes with increase in age. In spite of interindivividual variations, the RNFLT along both rings showed age-related changes in subjects.By neurobiological examinations, the experiments using monkey eyes showed that the glaucomatous optic nerve head expressed TGF-β more than that of normal in monkey eyes. This might be related progression of glaucomatous optic disc cupping. The glaucomatous monkey eyes showed lower expression of neurotrophins, NGF, BDNF and CNRF, instead higher expression of Trk B and CNTFR than those in normal eyes. Neurotrophic factors may relate with glaucoma induced optic nerve damage. In addition, degenerative mitochondria with disrupted outer membrane observed in swollen axons and higher expression of caspase 3 in the retinal nerve fiber layer seen in the rat experimental glaucoma model suggested possibility of the release of cytochrome c into cytosol which was known to behave as a critical switch in apoptotic cascade.