Ocular Application of Nerve Growth Factor Protects Degenerating Retinal Ganglion Cells in a Rat Model of Glaucoma

Ocular Application of Nerve Growth Factor Protects Degenerating Retinal Ganglion Cells in a Rat Model of Glaucoma
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DOI:
10.1097/ijg.0b013e3181d787e5
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发表时间:
2011-02-01
影响因子:
2
通讯作者:
Aloe, Luigi
Aloe, Luigi
中科院分区:
医学3区
文献类型:
--
作者:
Colafrancesco, Valeria;Parisi, Vincenzo;Aloe, Luigi

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目的:眼压升高是青光眼(GL)发展的重要病理事件。我们已经报道,神经生长因子(NGF)到达视网膜细胞和视神经(ON)时,适用于眼睛。是否眼部应用神经生长因子防止或减少视网膜神经节细胞(RGC)的损害是未知的。方法:GL诱导成年大鼠的右眼和左眼作为对照的巩膜外静脉注射高渗盐水。然后每天对大鼠眼部应用NGF或溶剂溶液进行治疗,持续7周。视网膜和ON组织,然后用于结构,免疫组化和生化studies.Results:高渗盐水注射到巩膜外静脉导致RGCs进行性变性,与近40%的这些细胞的损失后,7周的治疗。这种细胞损失与视网膜和ON的神经生长因子和神经生长因子受体表达的下调相关,并且用神经生长因子进行眼部治疗显著降低了由GL诱导的赤字。结论:这些研究结果表明,神经生长因子可以对发生在视网膜神经节细胞变性的视网膜神经节细胞发挥保护作用。我们认为,眼神经生长因子治疗可能是一个合适的药理学方法来研究保护机制的退化RGCs。
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.