Chung Hyewon, Lee Hyunju, Lamoke Folami, Hrushesky William J M, Wood Patricia A, Jahng Wan Jin
Department of Ophthalmology, Asan Medical Center, Seoul, Korea.
J Neurosci Res. 2009 Aug 1;87(10):2365-74. doi: 10.1002/jnr.22046.
Erythropoietin (EPO) stimulates red blood cell production, in part by inhibiting apoptosis of the red blood cell precursors. The erythropoietic effects of EPO are circadian stage dependent. Retinal injury due to light occurs through oxidative mechanisms and is manifest by retinal and retinal pigment epithelium (RPE) cells apoptosis. The visual cycle might be circadian coordinated as a means of effectively protecting the retina from the detrimental effects of light-induced, oxygen-dependent, free radical-mediated damage, especially at the times of day when light is more intense. We show that the retinal expression of EPO and its receptor (EPOR), as well as subsequent Janus kinase 2 (Jak2) phosphorylations, are each tightly linked to a specific time after oxidative stress and in anticipation of daily light onset. This is consistent with physiological protection against daily light-induced, oxidatively mediated retinal apoptosis. In vitro, we verify that EPO protects RPE cells from light, hyperoxia, and hydrogen peroxide-induced retinal cell apoptosis, and that these stimuli increase EPO and EPOR expression in cultured RPE cells. Together, these data support the premise that EPO and its EPOR interactions represent an important retinal shield from physiologic and pathologic light-induced oxidative injury.
促红细胞生成素（EPO）刺激红细胞生成，部分原因是通过抑制红细胞前体的凋亡。EPO的促红细胞生成作用具有昼夜节律阶段依赖性。光引起的视网膜损伤通过氧化机制发生，并表现为视网膜和视网膜色素上皮（RPE）细胞凋亡。视觉循环可能是昼夜节律协调的，以此作为一种有效保护视网膜免受光诱导、氧依赖性、自由基介导损伤的有害影响的手段，尤其是在一天中光线更强的时候。我们发现，EPO及其受体（EPOR）的视网膜表达，以及随后的Janus激酶2（Jak2）磷酸化，都与氧化应激后的特定时间紧密相关，并预期每日光照开始。这与针对每日光诱导、氧化介导的视网膜凋亡的生理保护作用一致。在体外，我们证实EPO可保护RPE细胞免受光、高氧和过氧化氢诱导的视网膜细胞凋亡，并且这些刺激会增加培养的RPE细胞中EPO和EPOR的表达。总之，这些数据支持这样一个前提，即EPO及其与EPOR的相互作用代表了视网膜免受生理和病理光诱导氧化损伤的重要屏障。
