Pease Mary Ellen, Zack Donald J, Berlinicke Cynthia, Bloom Kristen, Cone Frances, Wang Yuxia, Klein Ronald L, Hauswirth William W, Quigley Harry A
Department of Ophthalmology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, 175 Woods Research Building, Baltimore, MD 21287, USA.
Invest Ophthalmol Vis Sci. 2009 May;50(5):2194-200. doi: 10.1167/iovs.08-3013. Epub 2008 Dec 5.
To assess the neuroprotective effect of virally mediated overexpression of ciliary-derived neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in experimental rat glaucoma.
Laser-induced glaucoma was produced in one eye of 224 Wistar rats after injection of adenoassociated viral vectors (type 2) containing either CNTF, BDNF, or both, with saline-injected eyes and noninjected glaucomatous eyes serving as the control. IOP was measured with a hand-held tonometer, and semiautomated optic nerve axon counts were performed by masked observers. IOP exposure over time was adjusted in multivariate regression analysis to calculate the effect of CNTF and BDNF.
By multivariate regression, CNTF had a significant protective effect, with 15% less RGC axon death (P < 0.01). Both combined CNTF-BDNF and BDNF overexpression alone had no statistically significant improvement in RGC axon survival. By Western blot, there was a quantitative increase in CNTF and BDNF expression in retinas exposed to single viral vectors carrying each gene, but no increase with sequential injection of both vectors.
These data confirm that CNTF can exert a protective effect in experimental glaucoma. The reason for the lack of observed effect in the BDNF overexpression groups is unclear, but it may be a function of the level of neurotrophin expression achieved.
评估病毒介导的睫状神经营养因子（CNTF）和脑源性神经营养因子（BDNF）过表达对实验性大鼠青光眼的神经保护作用。
给224只Wistar大鼠的一只眼睛注射含CNTF、BDNF或两者的腺相关病毒载体（2型）后，诱导产生激光性青光眼，以注射生理盐水的眼睛和未注射的青光眼眼睛作为对照。用手持眼压计测量眼压，由不知情的观察者进行半自动视神经轴突计数。在多因素回归分析中对眼压随时间的变化进行调整，以计算CNTF和BDNF的作用。
通过多因素回归分析，CNTF具有显著的保护作用，视网膜神经节细胞（RGC）轴突死亡减少15%（P<0.01）。单独过表达CNTF-BDNF联合或BDNF均未使RGC轴突存活有统计学上的显著改善。通过蛋白质免疫印迹法，在暴露于携带每个基因的单一病毒载体的视网膜中，CNTF和BDNF表达有定量增加，但同时注射两种载体则无增加。
这些数据证实CNTF在实验性青光眼中可发挥保护作用。BDNF过表达组未观察到作用的原因尚不清楚，但可能与所达到的神经营养因子表达水平有关。
