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骨质疏松症相关蛋白缺乏小鼠的衰老视网膜。

The Retina of Osteopontin deficient Mice in Aging.

机构信息

Department of Cell Biology and Histology, University of Basque Country, www.ehu.es/GOBE, Experimental Ophtalmo-Biology Group UPV/EHU, Vizcaya, Spain.

Biocruces Research Institute, Barakaldo, Spain.

出版信息

Mol Neurobiol. 2018 Jan;55(1):213-221. doi: 10.1007/s12035-017-0734-9.

Abstract

Osteopontin (OPN) is a secreted glycosylated phosphoprotein that influences cell survival, inflammation, migration, and homeostasis after injury. As the role of OPN in the retina remains unclear, this study issue was addressed by aiming to study how the absence of OPN in knock-out mice affects the retina and the influence of age on these effects. The study focused on retinal ganglion cells (RGCs) and glial cells (astrocytes, Müller cells, and resident microglia) in 3- and 20-month-old mice. The number of RGCs in the retina was quantified and the area occupied by astrocytes was measured. In addition, the morphology of Müller cells and microglia was examined in retinal sections. The deficiency in OPN reduces RGC density by 25.09% at 3 months of age and by 60.37% at 20 months of age. The astrocyte area was also reduced by 51.01% in 3-month-old mice and by 57.84% at 20 months of age, although Müller glia and microglia did not seem to be affected by the lack of OPN. This study demonstrates the influence of OPN on astrocytes and RGCs, whereby the absence of OPN in the retina diminishes the area occupied by astrocytes and produces a secondary reduction in the number of RGCs. Accordingly, OPN could be a target to develop therapies to combat neurodegenerative diseases and astrocytes may represent a key mediator of such effects.

摘要

骨桥蛋白(OPN)是一种分泌型糖基化磷酸蛋白,可影响损伤后的细胞存活、炎症、迁移和稳态。由于 OPN 在视网膜中的作用尚不清楚,因此本研究旨在研究敲除小鼠中 OPN 的缺失如何影响视网膜以及年龄对这些影响的影响。该研究集中在视网膜神经节细胞(RGC)和神经胶质细胞(星形胶质细胞、Müller 细胞和常驻小胶质细胞)上,研究对象为 3 个月和 20 个月大的小鼠。定量了视网膜中 RGC 的数量,并测量了星形胶质细胞所占的面积。此外,还检查了视网膜切片中 Müller 细胞和小胶质细胞的形态。OPN 的缺乏使 3 个月大的小鼠的 RGC 密度降低了 25.09%,使 20 个月大的小鼠的 RGC 密度降低了 60.37%。3 个月大的小鼠中星形胶质细胞的面积也减少了 51.01%,20 个月大的小鼠中星形胶质细胞的面积减少了 57.84%,尽管 Müller 胶质细胞和小胶质细胞似乎不受 OPN 缺乏的影响。本研究表明 OPN 对星形胶质细胞和 RGC 有影响,视网膜中 OPN 的缺乏减少了星形胶质细胞所占据的面积,并导致 RGC 数量的继发性减少。因此,OPN 可能是开发治疗神经退行性疾病的靶点,而星形胶质细胞可能是这种作用的关键介导者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ac/5808060/d903e1221db3/12035_2017_734_Fig1_HTML.jpg

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