title: Rod-like microglia are restricted to eyes with laser-induced ocular hypertension but absent from the microglial changes in the contralateral untreated eye.
abstract: 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.
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Madrid, Spain ; Facultad de Óptica y Optometría, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: de Hoz
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Madrid, Spain ; Facultad de Óptica y Optometría, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Beatriz I
authors.initials: BI
authors.lastname: Gallego
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Madrid, Spain ; Facultad de Óptica y Optometría, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Ramírez
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Madrid, Spain ; Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Rojas
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Madrid, Spain ; Facultad de Óptica y Optometría, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Salazar
authors.affiliation: Department of Ophthalmology, School of Medicine, Murcia University, Murcia, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Valiente-Soriano
authors.affiliation: Department of Ophthalmology, School of Medicine, Murcia University, Murcia, Spain.
authors.forename: Marcelino
authors.initials: M
authors.lastname: Avilés-Trigueros
authors.affiliation: Department of Ophthalmology, School of Medicine, Murcia University, Murcia, Spain.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Villegas-Perez
authors.affiliation: Department of Ophthalmology, School of Medicine, Murcia University, Murcia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vidal-Sanz
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Madrid, Spain ; Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Triviño
authors.affiliation: Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Madrid, Spain ; Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Ramírez
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000528:radiation effects; D001369:Axons / Q000473:pathology / Q000528:radiation effects; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D007429:Intraocular Pressure / Q000528:radiation effects; D007834:Lasers / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D009798:Ocular Hypertension / Q000209:etiology* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000473:pathology*; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology*; D012590:Sclera / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects
chemical_list: C491049:Aif1 protein, mouse; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins