Rod-Like Microglia Are Restricted to Eyes with Laser-Induced Ocular Hypertension but Absent from the Microglial Changes in the Contralateral Untreated Eye

被引:78
作者
de Hoz, Rosa [1 ,2 ]
Gallego, Beatriz I. [1 ,2 ]
Ramirez, Ana I. [1 ,2 ]
Rojas, Blanca [1 ,3 ]
Salazar, Juan J. [1 ,2 ]
Valiente-Soriano, Francisco J. [4 ]
Aviles-Trigueros, Marcelino [4 ]
Villegas-Perez, Maria P. [4 ]
Vidal-Sanz, Manuel [4 ]
Trivino, Alberto [1 ,3 ]
Ramirez, Jose M. [1 ,3 ]
机构
[1] Univ Complutense Madrid, Inst Invest Oftalmol Ramon Castroviejo, Madrid, Spain
[2] Univ Complutense Madrid, Fac Opt & Optometria, Madrid, Spain
[3] Univ Complutense Madrid, Fac Med, Madrid, Spain
[4] Univ Murcia, Dept Ophthalmol, Sch Med, Murcia, Spain
关键词
ELEVATED INTRAOCULAR-PRESSURE; RETINAL GANGLION-CELLS; OPTIC-NERVE HEAD; GENE-EXPRESSION; HUMAN GLAUCOMA; RAT MODEL; INJURY; DEGENERATION; RESPONSES; ACTIVATION;
D O I
10.1371/journal.pone.0083733
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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 naive. 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 (naive, 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 naive 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.
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页数:19
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