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Microglia in mouse retina contralateral to experimental glaucoma exhibit multiple signs of activation in all retinal layers

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Rojas López, María Blanca and Gallego Collado, Beatriz Isabel and Ramírez Sebastián, Ana Isabel and Salazar Corral, Juan José and Hoz Montañana, María Rosa de and Valiente Soriano, Francisco Javier and Avilés Trigueros, Marcelino and Villegas Pérez, María Paz and Vidal Sanz, Manuel and Triviño Casado, Alberto (2014) Microglia in mouse retina contralateral to experimental glaucoma exhibit multiple signs of activation in all retinal layers. Journal of Neuroinflammation, 11 (1). nº 133. ISSN 1742-2094 (electrónico)

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Official URL: http://www.jneuroinflammation.com/content/11/1/133



Abstract

Background: Glaucomatous optic neuropathy, a leading cause of blindness, can progress despite control of intraocular pressure - currently the main risk factor and target for treatment. Glaucoma progression shares mechanisms with neurodegenerative disease, including microglia activation. In the present model of ocular hypertension (OHT), we have recently described morphological signs of retinal microglia activation and MHC-II upregulation in both the untreated contralateral eyes and OHT eyes. By using immunostaining, we sought to analyze and quantify additional signs of microglia activation and differences depending on the retinal layer. Methods: Two groups of adult Swiss mice were used: age-matched control (nai¨ve, n = 12), and lasered (n = 12). In the lasered animals, both OHT eyes and contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against Iba-1, MHC-II, CD68, CD86, and Ym1. The Iba-1+ cell number in the plexiform layers (PL) and the photoreceptor outer segment (OS), Iba-1+ arbor area in the PL, and area of the retina occupied by Iba-1+ cells in the nerve fiber layer-ganglion cell layer (NFL-GCL) were quantified. Results: The main findings in contralateral eyes and OHT eyes were: i) ameboid microglia in the NFL-GCL and OS; ii) the retraction of processes in all retinal layers; iii) a higher level of branching in PL and in the OS; iv) soma displacement to the nearest cell layers in the PL and OS; v) the reorientation of processes in the OS; vi) MHC-II upregulation in all retinal layers; vii) increased CD68 immunostaining; and viii) CD86 immunolabeling in ameboid cells. In comparison with the control group, a significant increase in the microglial number in the PL, OS, and in the area occupied by Iba-1+ cells in the NFL-GCL, and significant reduction of the arbor area in the PL. In addition, rounded Iba-1+ CD86+ cells in the NFL-GCL, OS and Ym1+ cells, and rod-like microglia in the NFL-GCL were restricted to OHT eyes. Conclusions: Several quantitative and qualitative signs of microglia activation are detected both in the contralateral and OHT eyes. Such activation extended beyond the GCL, involving all retinal layers. Differences between the two eyes could help to elucidate glaucoma pathophysiology.


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© 2014 Rojas et al.; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Uncontrolled Keywords:Microglia; Glaucoma; Retina; Mouse; Inflammation
Subjects:Medical sciences > Medicine > Ophtalmology
Medical sciences > Optics > Eyes anatomy
ID Code:31137
Deposited On:30 Jun 2015 08:40
Last Modified:07 Jul 2015 11:52

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