Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, Australia.
Invest Ophthalmol Vis Sci. 2011 Apr 22;52(5):2656-61. doi: 10.1167/iovs.10-6455.
Intrauterine infection is a common antecedent of preterm birth. Infants born very preterm are at increased risk for neurologic dysfunction, including visual deficits. With increasing survival of very preterm infants, there is a need for therapies that prevent adverse neurologic outcomes. Using an ovine model, the authors investigated the neuroprotective potential of recombinant human erythropoietin (rhEPO) on retinal injury induced by intrauterine inflammation.
At 107 ± 1 days of gestational age (DGA), chronically catheterized fetal sheep received either of the following on 3 consecutive days: intravenous (IV) bolus dose of lipopolysaccharide (LPS; ∼0.9 μg/kg; n = 8); IV bolus dose of LPS, followed at 1 hour by 5000 IU/kg rhEPO (LPS + rhEPO; n = 8); rhEPO alone (n = 5). Untreated fetuses (n = 8) were used for comparison with the three treatment groups. Fetal physiological parameters were monitored. At 116 ± 1 DGA, fetal retinas were assessed quantitatively for morphologic and neurochemical alterations.
Exposure to LPS alone, but not to rhEPO alone, resulted in fetal hypoxemia and hypotension (P < 0.05). Exposure to LPS alone caused retinal changes, including reductions in thickness of the inner nuclear layer (INL), somal areas of INL neurons, process growth in the plexiform layers, and numbers of ganglion and tyrosine hydroxylase immunoreactive (TH-IR) dopaminergic amacrine cells. Treatment of LPS-exposed fetuses with rhEPO did not alter the physiological effects of LPS but significantly reduced alterations in retinal layers and ganglion and TH-IR cell numbers.
rhEPO treatment was beneficial in protecting the developing retina after LPS-induced inflammation. Retinal protection could occur by the antiapoptotic or anti-inflammatory actions of EPO.
宫内感染是早产的常见诱因。极早产儿出生后患神经功能障碍的风险增加，包括视力缺陷。随着极早产儿存活率的提高，需要寻找能够预防不良神经结局的治疗方法。作者使用绵羊模型研究了重组人红细胞生成素（rhEPO）对宫内炎症引起的视网膜损伤的神经保护作用。
在妊娠 107±1 天（GA），对长期置管的胎儿绵羊连续 3 天给予以下处理：静脉内（IV）给予脂多糖（LPS；约 0.9μg/kg；n=8）；IV 给予 LPS 后 1 小时给予 5000IU/kg rhEPO（LPS+rhEPO；n=8）；单独给予 rhEPO（n=5）。未治疗的胎儿（n=8）用于与三组治疗进行比较。监测胎儿生理参数。在 116±1 GA 时，定量评估胎儿视网膜的形态和神经化学改变。
单独给予 LPS 会导致胎儿低氧血症和低血压（P<0.05），但单独给予 rhEPO 不会。单独给予 LPS 会引起视网膜改变，包括内核层（INL）厚度减少、INL 神经元体面积减少、神经纤维层的突起生长减少以及节细胞和酪氨酸羟化酶免疫反应性（TH-IR）多巴胺能无长突细胞数量减少。用 rhEPO 治疗 LPS 暴露的胎儿并没有改变 LPS 的生理作用，但显著减少了视网膜层和节细胞及 TH-IR 细胞数量的改变。
rhEPO 治疗对 LPS 诱导的炎症后发育中的视网膜有益。EPO 的抗凋亡或抗炎作用可能导致视网膜保护。
