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Effects of age on retinal macrophage responses to acute elevation of intraocular pressure
Experimental Eye Research ( IF 3.0 ) Pub Date : 2020-03-07 , DOI: 10.1016/j.exer.2020.107995
Jelena M. Kezic , Vicki Chrysostomou , Paul G. McMenamin , Jonathan G. Crowston

There is accumulating evidence that aging shifts the central nervous system milieu towards a proinflammatory state, with increased reactivity of microglia in the aging eye and brain having been implicated in the development of age-related neurodegenerative conditions. Indeed, alterations to microglial morphology and function have been recognized as a part of normal aging. Here, we sought to assess the effects of age on the retinal microglial and macrophage response to acute intraocular pressure (IOP) elevation. Further, we performed experiments whereby bone marrow from young or middle-aged mice was used to reconstitute the bone marrow of whole-body irradiated 12 month old mice. Bone marrow chimeric mice then underwent cannulation and IOP elevation 8 weeks after whole-body irradiation and bone marrow transplantation in order to determine whether the age of bone marrow alters the macrophage response to retinal injury. Our data show retinal macrophage reactivity and microglial morphological changes were enhanced in older mice when compared to younger mice in response to injury. When IOP elevation was performed after whole-body irradiation and bone marrow rescue, we noted subretinal macrophage accumulation and glial reactivity was reduced compared to non-irradiated mice that had also undergone IOP elevation. This effect was evident in both groups of chimeric mice that had received either young or middle-aged bone marrow, suggesting irradiation itself may alter the macrophage and glial response to injury rather than the age of bone marrow.



中文翻译:

年龄对视网膜巨噬细胞对急性眼内压升高反应的影响

越来越多的证据表明,衰老使中枢神经系统环境向促炎状态转变,其中衰老的眼睛和大脑中的小胶质细胞的反应性增加与年龄相关的神经退行性疾病的发展有关。实际上,小胶质细胞形态和功能的改变已被认为是正常衰老的一部分。在这里,我们试图评估年龄对视网膜小胶质细胞和巨噬细胞对急性眼内压(IOP)升高的反应的影响。此外,我们进行了实验,用年轻或中年小鼠的骨髓重建了全身照射的12个月大小鼠的骨髓。然后,在全身照射和骨髓移植后8周,对骨髓嵌合小鼠进行插管和IOP升高,以确定骨髓的年龄是否会改变巨噬细胞对视网膜损伤的反应。我们的数据显示,与损伤的年轻小鼠相比,老年小鼠的视网膜巨噬细胞反应性和小胶质细胞形态变化得到增强。当在全身照射和骨髓抢救后进行IOP升高时,我们注意到与也经历了IOP升高的未辐照小鼠相比,视网膜下巨噬细胞积累和神经胶质反应性降低。在接受过年轻或中年骨髓的两组嵌合小鼠中,这种效果都很明显,

更新日期:2020-03-09
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