Department of Ophthalmology, Eye Institute of China PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Ophthalmology, Jinling Hospital, Nanjing, China.
Sci Rep. 2017 Aug 8;7(1):7535. doi: 10.1038/s41598-017-07978-z.
The role of microglia in the pathophysiology of ischemic retinal diseases has been extensively studied. Retinal microglial activation may be correlated with retinal neovascularization in oxygen-induced retinopathy (OIR), an animal model that has been widely used in retinopathy of prematurity (ROP) research. Minocycline is an antibiotic that decreases microglial activation following hyperoxic and hypoxic-ischemic phases in neonatal rodents. Here, we investigated the effects of minocycline on vascularization and visual function. In our results, we found that after the administration of minocycline, microglial reactivity was reduced in the retina, which was accompanied by an increase in the avascular area at P12, P14 and P17. Although microglial reactivity was reduced at P17, minocycline treatment did not attenuate retinal neovascularization. A changing trend in microglial number was observed, and the apoptosis and proliferation states on different days partly contributed to this change. Further study also revealed that although minocycline downregulated the levels of proinflammatory factors, visual function appeared to be significantly worsened. Collectively, we demonstrated that minocycline disturbed the physiological vascularization of the avascular area and exacerbated visual dysfunction, indicating that minocycline may not be an effective drug and may even be detrimental for the treatment of ischemic retinopathy in immature mammals.
小胶质细胞在缺血性视网膜疾病的病理生理学中的作用已经得到了广泛的研究。视网膜小胶质细胞的激活可能与氧诱导的视网膜病变(OIR)中的视网膜新生血管化有关,OIR 是一种在早产儿视网膜病变(ROP)研究中广泛应用的动物模型。米诺环素是一种抗生素,可减少新生鼠在高氧和缺氧缺血期后的小胶质细胞激活。在这里,我们研究了米诺环素对血管生成和视觉功能的影响。在我们的结果中,我们发现米诺环素给药后,视网膜中小胶质细胞的反应性降低,同时 P12、P14 和 P17 时无血管区面积增加。尽管 P17 时小胶质细胞的反应性降低,但米诺环素治疗并未减轻视网膜新生血管化。观察到小胶质细胞数量的变化趋势,不同天数的凋亡和增殖状态部分导致了这种变化。进一步的研究还表明,尽管米诺环素下调了促炎因子的水平,但视觉功能似乎明显恶化。总之,我们证明米诺环素扰乱了无血管区的生理性血管生成,并加重了视觉功能障碍,表明米诺环素可能不是一种有效的药物,甚至可能对治疗未成熟哺乳动物的缺血性视网膜病变有害。