de Hoz Rosa, Gallego Beatriz I, Ramírez Ana I, Rojas Blanca, Salazar Juan J, Valiente-Soriano Francisco J, Avilés-Trigueros Marcelino, Villegas-Perez Maria P, Vidal-Sanz Manuel, Triviño Alberto, Ramírez José M
Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Madrid, Spain ; Facultad de Óptica y Optometría, Universidad Complutense de Madrid, Madrid, Spain.
Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Madrid, Spain ; Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
PLoS One. 2013 Dec 18;8(12):e83733. doi: 10.1371/journal.pone.0083733. eCollection 2013.
In the mouse model of unilateral laser-induced ocular hypertension (OHT) the microglia in both the treated and the normotensive untreated contralateral eye have morphological signs of activation and up-regulation of MHC-II expression in comparison with naïve. In the brain, rod-like microglia align to less-injured neurons in an effort to limit damage. We investigate whether: i) microglial activation is secondary to laser injury or to a higher IOP and; ii) the presence of rod-like microglia is related to OHT. Three groups of mice were used: age-matched control (naïve, n=15); and two lasered: limbal (OHT, n=15); and non-draining portion of the sclera (scleral, n=3). In the lasered animals, treated eyes as well as contralateral eyes were analysed. Retinal whole-mounts were immunostained with antibodies against, Iba-1, NF-200, MHC-II, CD86, CD68 and Ym1. In the scleral group (normal ocular pressure) no microglial signs of activation were found. Similarly to naïve eyes, OHT-eyes and their contralateral eyes had ramified microglia in the nerve-fibre layer related to the blood vessel. However, only eyes with OHT had rod-like microglia that aligned end-to-end, coupling to form trains of multiple cells running parallel to axons in the retinal surface. Rod-like microglia were CD68+ and were related to retinal ganglion cells (RGCs) showing signs of degeneration (NF-200+RGCs). Although MHC-II expression was up-regulated in the microglia of the NFL both in OHT-eyes and their contralateral eyes, no expression of CD86 and Ym1 was detected in ramified or in rod-like microglia. After 15 days of unilateral lasering of the limbal and the non-draining portion of the sclera, activated microglia was restricted to OHT-eyes and their contralateral eyes. However, rod-like microglia were restricted to eyes with OHT and degenerated NF-200+RGCs and were absent from their contralateral eyes. Thus, rod-like microglia seem be related to the neurodegeneration associated with HTO.
在单侧激光诱导性高眼压（OHT）小鼠模型中，与未处理的正常对侧眼相比，处理眼和未处理的正常对侧眼的小胶质细胞均有活化的形态学迹象以及MHC-II表达上调。在大脑中，杆状小胶质细胞排列在损伤较轻的神经元周围，以限制损伤。我们研究：i）小胶质细胞活化是继发于激光损伤还是更高的眼压；ii）杆状小胶质细胞的存在是否与高眼压有关。使用了三组小鼠：年龄匹配的对照组（未处理，n = 15）；两组激光处理组：角膜缘（高眼压，n = 15）；巩膜非引流部分（巩膜，n = 3）。对激光处理的动物，分析处理眼以及对侧眼。视网膜全层标本用抗Iba-1、NF-200、MHC-II、CD86、CD68和Ym1的抗体进行免疫染色。在巩膜组（正常眼压）未发现小胶质细胞活化迹象。与未处理眼类似，高眼压眼及其对侧眼在与血管相关的神经纤维层中有分支状小胶质细胞。然而，只有高眼压眼有杆状小胶质细胞，它们首尾相连，连接形成多个细胞的链，与视网膜表面的轴突平行排列。杆状小胶质细胞为CD68阳性，与显示变性迹象（NF-200阳性视网膜神经节细胞）的视网膜神经节细胞（RGCs）相关。尽管高眼压眼及其对侧眼的神经纤维层中小胶质细胞的MHC-II表达上调，但在分支状或杆状小胶质细胞中未检测到CD86和Ym1的表达。在角膜缘和巩膜非引流部分单侧激光照射15天后，活化的小胶质细胞局限于高眼压眼及其对侧眼。然而，杆状小胶质细胞局限于高眼压眼以及变性的NF-200阳性视网膜神经节细胞，在其对侧眼中不存在。因此，杆状小胶质细胞似乎与高眼压相关的神经退行性变有关。
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