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

临床研究总结：采用扫描式激光偏振仪对60例正常人120只眼的视网膜神经纤维层厚度进行了测量。沿直径1.75椎间盘直径的乳头周围环和距椎间盘边缘0.8 mm的乳头周围环测量。沿两个环的RNFLT与年龄无显著相关。然而，RNFLT的总/鼻面积比值随着年龄的增加而显著降低。两眼RNFLT差异随年龄增加而增加。尽管个体间存在差异，但两个环上的RNFLT在受试者中显示出与年龄相关的变化。经神经生物学检查，猴眼实验发现，青光眼视神经头TGF-β表达高于正常猴眼。这可能与青光眼视盘拔火罐的进展有关。青光眼猴眼神经营养因子、NGF、BDNF和CNRF的表达低于正常眼，Trk B和CNTFR的表达高于正常眼。神经营养因子可能与青光眼引起的视神经损伤有关。此外，在肿胀的轴突中观察到外膜破坏的退行性线粒体，在大鼠实验性青光眼模型中观察到视网膜神经纤维层中caspase 3的高表达，表明细胞色素c可能释放到细胞质中，这是已知的凋亡级联的关键开关。

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.