Alleviation of constant-light-induced photoreceptor degeneration by adaptation of adult albino rat to bright cyclic light
Alleviation of constant-light-induced photoreceptor degeneration by adaptation of adult albino rat to bright cyclic light
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DOI：
10.1167/iovs.03-0140
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发表时间：
2003-11-01
影响因子：
4.4
通讯作者：
Anderson, RE
中科院分区：
文献类型：
--
作者：
Li, F;Cao, W;Anderson, RE
目的。为了进一步验证战斗适应介导的光感受器保护通过激活和/或上调神经保护分子来抑制细胞凋亡的假设。方法：出生和长大的白化大鼠在5勒克斯的周期性战斗中(断断续续地12小时)。在8周龄时，动物适应了不同时期的400勒克斯周期战斗。在1700Lux照度下连续战斗1d，可引起光损伤。动物被杀，并摘除它们的眼睛进行形态测量和生化分析。TUNEL法检测光感受器细胞的凋亡，Western印迹法检测碱性成纤维细胞生长因子(BFGF)、神经元型一氧化氮合酶(NNOS)和半胱氨酸天冬氨酸氨基转移酶-3(caspase-3)的表达。适应400勒克斯明亮的周期性战斗4天后，持续光照诱导的TUNEL阳性细胞显著减少，这与碱性成纤维细胞生长因子表达显著增加有关。与对照视网膜相比，caspase-3水平不受恒定光照或400lux适应后的影响。恒光暴露组大鼠视网膜nNOS水平显著升高，而适应400lux强光后再恒光暴露组则无明显变化。结论：成年大鼠视网膜从暗循环状态转换为亮周期状态时，可迅速上调神经保护机制。识别参与这一过程的分子可能有助于合理开发治疗视网膜退行性疾病的方法。
PURPOSE. To further test the hypothesis that fight-adaptation-mediated photoreceptor protection works through inhibition of apoptosis by activation and/or upregulation of neuroprotective molecules.METHODS. Albino rats were born and raised in 5-lux cyclic fight (12 hours OFF and ON). At 8 weeks of age, animals were adapted to 400-lux cyclic fight for different periods. Light damage was induced by exposure to constant fight for I day at an illumination of 1700 lux. Animals were killed, and their eyes were removed for morphometric and biochemical analysis. TUNEL assay was used to evaluate photoreceptor cell apoptosis and Western blot analyses were used to determine the levels of basic fibroblast growth factor (bFGF), neuronal nitric oxide synthase (nNOS), and caspase-3.RESULTS. Exposure of dim-reared rats to constant fight for 1 day dramatically increased TUNEL-positive cells in the outer nuclear layer. Adaptation to 400-lux bright cyclic fight for 4 days significantly reduced TUNEL-positive cells induced by exposure to constant light, which correlated with a significant increase in bFGF expression. Compared with control retinas, caspase-3 levels were not changed by exposure to constant light or after adaptation to 400 lux. There was a significant increase in nNOS level in the constant-light- exposed group, but not in the group adapted to 400-lux bright light before exposure to constant light.CONCLUSIONS. The retina of the adult rat can rapidly upregulate neuroprotective mechanisms when switched from dim to bright cyclic fight. Identification of the molecules involved in this process may allow rational development of therapeutic approaches to treat retinal degenerative diseases.