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神经营养因子滴眼对青光眼大鼠模型变性视网膜神经节细胞的保护作用。

Ocular application of nerve growth factor protects degenerating retinal ganglion cells in a rat model of glaucoma.

机构信息

Department of Ophthalmology, IRCCS, G.B. Bietti Eye Foundation, Rome, Italy.

出版信息

J Glaucoma. 2011 Feb;20(2):100-8. doi: 10.1097/IJG.0b013e3181d787e5.

Abstract

PURPOSE

Elevated intraocular pressure is a crucial pathologic event for the development of glaucoma (GL). We have reported that nerve growth factor (NGF) reaches retinal cells and the optic nerve (ON) when applied to the eye. Whether ocular application of NGF prevents or reduces damage to retinal ganglion cell (RGC) is not known.

METHODS

GL was induced in adult rats by the injection of hypertonic saline into the episcleral vein of the right eye and the left eye used as control. Rats were then treated daily with ocular application of NGF or vehicle solution for 7 weeks. Retinal and ON tissues were then used for structural, immunohistochemical, and biochemical studies.

RESULTS

The injection of hypertonic saline into the episcleral vein led to progressive degeneration of RGCs, with the loss of nearly 40% of these cells after 7 weeks of treatment. This cellular loss is associated with the downregulation of NGF and NGF-receptor expression in the retina and ON of the glaucomatous eye and ocular treatment with NGF significantly reduced the deficit induced by GL.

CONCLUSIONS

These findings indicate that NGF can exert protective action on RGC degeneration occurring in glaucomatous retina. We suggest that ocular NGF treatment might be a suitable pharmacologic approach to investigate protective mechanisms of degenerating RGCs.

摘要

目的

眼内压升高是青光眼(GL)发展的关键病理事件。我们已经报告过,神经生长因子(NGF)在应用于眼睛时会到达视网膜细胞和视神经(ON)。目前尚不清楚眼部应用 NGF 是否可以预防或减少对视网膜神经节细胞(RGC)的损伤。

方法

通过向右眼巩膜静脉内注射高渗盐水诱导成年大鼠发生 GL,左眼作为对照。然后,大鼠每天接受眼部 NGF 或载体溶液治疗 7 周。然后使用视网膜和 ON 组织进行结构、免疫组织化学和生化研究。

结果

向巩膜静脉内注射高渗盐水导致 RGC 进行性退化,经过 7 周的治疗后,这些细胞几乎损失了 40%。这种细胞丢失与青光眼眼中视网膜和 ON 中 NGF 和 NGF 受体表达的下调有关,而眼部应用 NGF 可显著减少 GL 引起的不足。

结论

这些发现表明,NGF 可以对青光眼视网膜中发生的 RGC 变性发挥保护作用。我们建议眼部 NGF 治疗可能是研究变性 RGC 保护机制的一种合适的药物治疗方法。

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