Jomary Catherine, Darrow Ruth M, Wong Paul, Organisciak Daniel T, Jones Stephen E
Division of Biomolecular Sciences, GKT School of Biomedical Sciences, King's College London, St. Thomas' Hospital, London, United Kingdom.
Invest Ophthalmol Vis Sci. 2004 Apr;45(4):1240-6. doi: 10.1167/iovs.03-1122.
Dysregulation of neurturin (NTN) expression has been linked to photoreceptor apoptosis in a mouse model of inherited retinal degeneration. To investigate the extent to which any such dysregulation depends on the nature of the apoptotic trigger, the expression of NTN, glial cell line-derived neurotrophic factor (GDNF), and their corresponding receptor components were compared in a rat model of light-induced retinal degeneration.
Retinal expression of NTN, GDNF, their corresponding receptors GFRalpha-2 and -1, the transmembrane receptor tyrosine kinase (Ret), and cSrc-p60, a member of the cytoplasmic protein-tyrosine kinases family, were analyzed by Western blot analysis and immunocytochemistry in cyclic light- and dark-reared rats in the presence and absence of intense light exposure.
All components for NTN-mediated signaling activation are present in rat photoreceptors and retinal pigment epithelium, the cells primarily affected by light-induced damage. The expression levels of GDNF, its receptor components, and NTN, were not affected by light-induced stress. However, GFRalpha-2 expression strikingly increased with the extent of retinal damage, especially at the photoreceptors, in contrast to decreased levels that were observed previously in an inherited degeneration model.
The present study indicates that the expression of receptors of the GDNF family is independently regulated in normal and light-damaged rat retina, and in conjunction with previous work, suggests that the pattern of modulation of these genes during photoreceptor degeneration is determined by the nature of the apoptotic trigger. Such differential responses to different modes of retinal degeneration may reflect influences of the neurotrophic system on photoreceptor survival or in the regulation of neuronal plasticity.
在遗传性视网膜变性小鼠模型中，神经营养因子（NTN）表达失调与光感受器凋亡有关。为了研究这种失调在多大程度上取决于凋亡触发因素的性质，在光诱导的视网膜变性大鼠模型中比较了NTN、胶质细胞系源性神经营养因子（GDNF）及其相应受体成分的表达。
通过蛋白质免疫印迹分析和免疫细胞化学方法，分析了在有或无强光照射情况下，正常昼夜交替饲养和持续光照饲养的大鼠视网膜中NTN、GDNF、它们相应的受体GFRalpha-2和-1、跨膜受体酪氨酸激酶（Ret）以及细胞质蛋白酪氨酸激酶家族成员cSrc-p60的表达情况。
NTN介导的信号激活的所有成分都存在于大鼠光感受器和视网膜色素上皮中，这些细胞是受光诱导损伤影响的主要细胞。GDNF及其受体成分以及NTN的表达水平不受光诱导应激的影响。然而，与先前在遗传性变性模型中观察到的水平降低相反，GFRalpha-2的表达随着视网膜损伤程度的增加而显著增加，尤其是在光感受器处。
本研究表明，在正常和光损伤的大鼠视网膜中，GDNF家族受体的表达是独立调节的，并且结合先前的研究工作表明，在光感受器变性过程中这些基因的调节模式是由凋亡触发因素的性质决定的。对不同视网膜变性模式的这种差异反应可能反映了神经营养系统对光感受器存活或神经元可塑性调节的影响。
