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Bilateral early activation of retinal microglial cells in a mouse model of unilateral laser-induced experimental ocular hypertension.
Exp Eye Res. 2018 06; 171:12-29.EE

Abstract

The immune system plays an important role in glaucomatous neurodegeneration. Retinal microglial reactivation associated with ganglion cell loss could reportedly contribute to the glaucoma progression. Recently we have described signs of microglia activation both in contralateral and ocular hypertension (OHT) eyes involving all retinal layers 15 days after OHT laser induction in mice. However, no works available have analyzed the microglial activation at earliest time points after OHT induction (24 h) in this experimental model. Thus, we seek to describe and quantify signs of microglia activation and differences depending on the retinal layer, 24 h after unilateral laser-induced OHT. Two groups of adult Swiss mice were used: age-matched control (naïve) and lasered. In the lasered animals, OHT eyes as well as contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against Iba-1 and MHC-II. We quantified the number of microglial cells in the photoreceptor layer (OS), outer plexiform layer (OPL), and inner plexiform layer (IPL); the number of microglial vertical processes connecting the OPL and OS; the area of the retina occupied by Iba-1+ cells (Iba1-RA) in the nerve fiber layer-ganglion cell layer (NFL-GCL), the total arbor area of microglial cells in the OPL and IPL and; Iba-1+ cell body area in the OPL, IPL and NFL-GCL. In contralateral and OHT eyes the morphological features of Iba-1+ cell activation were: migration, enlargement of the cell body, higher degree of branching and reorientation of the processes, radial disposition of the soma and processes toward adjacent microglial plexuses, and presence of amoeboid cells acting as macrophages. These signs were more pronounced in OHT eyes. Most of Iba-1+ cells did not express MHC-II; rather, only dendritic and rounded cells expressed it. In comparison with naïve eyes, in OHT eyes and contralateral eyes no significant differences were found in the microglial cell number; but there was a significant increase in Iba1-RA. The total arbor area of microglial cells was significantly decreased in: i) OHT eyes with respect contralateral eyes and naïve-eyes in IPL; ii) OHT eyes with respect to naïve eyes in OPL. The number of microglial vertical processes connecting the OPL and OS were significantly increased in contralateral eyes compared with naïve-eyes and OHT eyes. In OPL, IPL and NFL-GCL, the cell body area of Iba-1+ cells was significantly greater in OHT eyes than in naïve and contralateral eyes, and greater in contralateral eyes than in naïve eyes. A non-proliferative microglial reactivation was detected both in contralateral eyes and in OHT eyes in an early time after unilateral laser-induced OHT (24 h). This fast microglial activation, which involves the contralateral eye, could be mediated by the immune system.

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Authors+Show Affiliations

de Hoz R
Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Spain; Facultad de Óptica y Optometría, Departamento de Inmunología, Oftalmología y ORL, Universidad Complutense de Madrid, Spain. Electronic address: rdehoz@med.ucm.es.
Ramírez AI
Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Spain; Facultad de Óptica y Optometría, Departamento de Inmunología, Oftalmología y ORL, Universidad Complutense de Madrid, Spain. Electronic address: airamirez@med.ucm.es.
González-Martín R
Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Spain. Electronic address: rosagonz@ucm.es.
Ajoy D
Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Spain. Electronic address: dajoym@gmail.com.
Rojas B
Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Spain; Facultad de Medicina, Departamento de Inmunología, Oftalmología y ORL, Universidad Complutense de Madrid, Spain. Electronic address: brojas@med.ucm.es.
Salobrar-Garcia E
Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Spain; Facultad de Medicina, Departamento de Inmunología, Oftalmología y ORL, Universidad Complutense de Madrid, Spain. Electronic address: elenasalobrar@med.ucm.es.
Valiente-Soriano FJ
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca, Murcia, Spain. Electronic address: fjvaliente@um.es.
Avilés-Trigueros M
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca, Murcia, Spain. Electronic address: marcelin@um.es.
Villegas-Pérez MP
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca, Murcia, Spain. Electronic address: mpville@um.es.
Vidal-Sanz M
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca, Murcia, Spain. Electronic address: manuel.vidal@um.es.
Triviño A
Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Spain; Facultad de Medicina, Departamento de Inmunología, Oftalmología y ORL, Universidad Complutense de Madrid, Spain. Electronic address: atrivino@med.ucm.es.
Ramírez JM
Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Spain; Facultad de Medicina, Departamento de Inmunología, Oftalmología y ORL, Universidad Complutense de Madrid, Spain. Electronic address: ramirezs@med.ucm.es.
Salazar JJ
Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Spain; Facultad de Óptica y Optometría, Departamento de Inmunología, Oftalmología y ORL, Universidad Complutense de Madrid, Spain. Electronic address: jjsalazar@med.ucm.es.

MeSH

AnimalsCalcium-Binding ProteinsCell CountDisease Models, AnimalFluorescent Antibody Technique, IndirectHistocompatibility Antigens Class IIIntraocular PressureLaser CoagulationMaleMiceMicrofilament ProteinsMicrogliaNerve FibersOcular HypertensionRetinaRetinal Ganglion CellsTonometry, Ocular

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29526796

Citation

de Hoz, Rosa, et al. "Bilateral Early Activation of Retinal Microglial Cells in a Mouse Model of Unilateral Laser-induced Experimental Ocular Hypertension." Experimental Eye Research, vol. 171, 2018, pp. 12-29.
de Hoz R, Ramírez AI, González-Martín R, et al. Bilateral early activation of retinal microglial cells in a mouse model of unilateral laser-induced experimental ocular hypertension. Exp Eye Res. 2018;171:12-29.
de Hoz, R., Ramírez, A. I., González-Martín, R., Ajoy, D., Rojas, B., Salobrar-Garcia, E., Valiente-Soriano, F. J., Avilés-Trigueros, M., Villegas-Pérez, M. P., Vidal-Sanz, M., Triviño, A., Ramírez, J. M., & Salazar, J. J. (2018). Bilateral early activation of retinal microglial cells in a mouse model of unilateral laser-induced experimental ocular hypertension. Experimental Eye Research, 171, 12-29. https://doi.org/10.1016/j.exer.2018.03.006
de Hoz R, et al. Bilateral Early Activation of Retinal Microglial Cells in a Mouse Model of Unilateral Laser-induced Experimental Ocular Hypertension. Exp Eye Res. 2018;171:12-29. PubMed PMID: 29526796.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bilateral early activation of retinal microglial cells in a mouse model of unilateral laser-induced experimental ocular hypertension. AU - de Hoz,Rosa, AU - Ramírez,Ana I, AU - González-Martín,Rosa, AU - Ajoy,Daniel, AU - Rojas,Blanca, AU - Salobrar-Garcia,Elena, AU - Valiente-Soriano,Francisco J, AU - Avilés-Trigueros,Marcelino, AU - Villegas-Pérez,Maria P, AU - Vidal-Sanz,Manuel, AU - Triviño,Alberto, AU - Ramírez,José M, AU - Salazar,Juan J, Y1 - 2018/03/09/ PY - 2017/10/04/received PY - 2018/02/23/revised PY - 2018/03/07/accepted PY - 2018/3/13/pubmed PY - 2018/12/24/medline PY - 2018/3/13/entrez KW - Contralateral KW - Early activation KW - Experimental glaucoma KW - Iba-1 KW - MHC-II KW - Microglia KW - Ocular hypertension KW - Retina SP - 12 EP - 29 JF - Experimental eye research JO - Exp Eye Res VL - 171 N2 - The immune system plays an important role in glaucomatous neurodegeneration. Retinal microglial reactivation associated with ganglion cell loss could reportedly contribute to the glaucoma progression. Recently we have described signs of microglia activation both in contralateral and ocular hypertension (OHT) eyes involving all retinal layers 15 days after OHT laser induction in mice. However, no works available have analyzed the microglial activation at earliest time points after OHT induction (24 h) in this experimental model. Thus, we seek to describe and quantify signs of microglia activation and differences depending on the retinal layer, 24 h after unilateral laser-induced OHT. Two groups of adult Swiss mice were used: age-matched control (naïve) and lasered. In the lasered animals, OHT eyes as well as contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against Iba-1 and MHC-II. We quantified the number of microglial cells in the photoreceptor layer (OS), outer plexiform layer (OPL), and inner plexiform layer (IPL); the number of microglial vertical processes connecting the OPL and OS; the area of the retina occupied by Iba-1+ cells (Iba1-RA) in the nerve fiber layer-ganglion cell layer (NFL-GCL), the total arbor area of microglial cells in the OPL and IPL and; Iba-1+ cell body area in the OPL, IPL and NFL-GCL. In contralateral and OHT eyes the morphological features of Iba-1+ cell activation were: migration, enlargement of the cell body, higher degree of branching and reorientation of the processes, radial disposition of the soma and processes toward adjacent microglial plexuses, and presence of amoeboid cells acting as macrophages. These signs were more pronounced in OHT eyes. Most of Iba-1+ cells did not express MHC-II; rather, only dendritic and rounded cells expressed it. In comparison with naïve eyes, in OHT eyes and contralateral eyes no significant differences were found in the microglial cell number; but there was a significant increase in Iba1-RA. The total arbor area of microglial cells was significantly decreased in: i) OHT eyes with respect contralateral eyes and naïve-eyes in IPL; ii) OHT eyes with respect to naïve eyes in OPL. The number of microglial vertical processes connecting the OPL and OS were significantly increased in contralateral eyes compared with naïve-eyes and OHT eyes. In OPL, IPL and NFL-GCL, the cell body area of Iba-1+ cells was significantly greater in OHT eyes than in naïve and contralateral eyes, and greater in contralateral eyes than in naïve eyes. A non-proliferative microglial reactivation was detected both in contralateral eyes and in OHT eyes in an early time after unilateral laser-induced OHT (24 h). This fast microglial activation, which involves the contralateral eye, could be mediated by the immune system. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/29526796/Bilateral_early_activation_of_retinal_microglial_cells_in_a_mouse_model_of_unilateral_laser_induced_experimental_ocular_hypertension_ DB - PRIME DP - Unbound Medicine ER -