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Assessment of inner retina dysfunction and progressive ganglion cell loss in a mouse model of glaucoma.
Exp Eye Res. 2014 May; 122:40-9.EE

Abstract

The DBA/2J mouse is a model of ocular hypertension and retinal ganglion cell (RGC) degeneration, the main features of which are iris pigment dispersion (IPD) and iris stromal atrophy (ISA). These animals also experience glaucomatous changes, including an increase in intraocular pressure (IOP) beginning at about 9-12 months of age and sectorial RGC death in the retina. The aim of this study was to determine the onset of functional changes exhibited by DBA/2J mice in the inner retina. This was performed by means of electroretinographic recordings (scotopic threshold response, STR) and their correlation with morphological changes (loss of RGCs). To this end, we recorded the scotopic threshold response in control C57BL/6J and in DBA/2J mice at different ages. The RGCs, in both DBA/2J and C57BL/6J animals, were identified at 15 months of age by retrograde tracing with an analogue of fluorogold, hydroxystilbamidine methanesulfonate (OHSt), applied on the superior colliculi. Whole mount retinas were processed to quantify the population of RGCs identified by fluorogold tracing and Brn3a immunodetection, and were counted using image analysis software; an isodensity contour plot was generated for each retina. DBA/2J mice showed a significant reduction in the positive STR (pSTR) amplitudes at 12 months of age, as compared to control C57BL/6J mice of the same age. The pSTR mean amplitude decreased to approximately 27.82% of the values recorded in control mice (p = 0.0058). STR responses decreased in both strains as a result of the natural process of aging, but the decrease was more pronounced in DBA/2J mice. Furthermore, quantification of the total number of RGCs identified by OHSt and Brn3a expression showed a reduced population of RGCs in DBA/2J mice as compared to control mice. Regression analysis revealed significant correlations between the decrease in pSTR and a non-homogeneous reduction in the number of RGCs throughout the retina. Our results indicate the existence of a correlation between retinal function impairment and RGC loss. This functional and morphological analysis allows a reliable assessment of the progression of the disease.

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Authors+Show Affiliations

Pérez de Lara MJ
Department of Biochemistry and Molecular Biology IV, Faculty of Optics and Optometry, Complutense University of Madrid, c/Arcos de Jalón 118, E-28037 Madrid, Spain; Red Española Temática de Investigación Cooperativa en Patología Ocular Prevalente y Crónica, Instituto de Salud Carlos III, Madrid, PC, Spain.
Santano C
Department of Biochemistry and Molecular Biology IV, Faculty of Optics and Optometry, Complutense University of Madrid, c/Arcos de Jalón 118, E-28037 Madrid, Spain.
Guzmán-Aránguez A
Department of Biochemistry and Molecular Biology IV, Faculty of Optics and Optometry, Complutense University of Madrid, c/Arcos de Jalón 118, E-28037 Madrid, Spain; Red Española Temática de Investigación Cooperativa en Patología Ocular Prevalente y Crónica, Instituto de Salud Carlos III, Madrid, PC, Spain.
Valiente-Soriano FJ
Experimental Ophthalmology Laboratory, Dept. of Ophthalmology, College of Medicine, University of Murcia, Regional Campus of International Excellence "Campus Mare Nostrum", Murcia Institute of Bio-Health Research (IMIB), E-30100 Murcia, Spain; Red Española Temática de Investigación Cooperativa en Patología Ocular Prevalente y Crónica, Instituto de Salud Carlos III, Madrid, PC, Spain.
Avilés-Trigueros M
Experimental Ophthalmology Laboratory, Dept. of Ophthalmology, College of Medicine, University of Murcia, Regional Campus of International Excellence "Campus Mare Nostrum", Murcia Institute of Bio-Health Research (IMIB), E-30100 Murcia, Spain; Red Española Temática de Investigación Cooperativa en Patología Ocular Prevalente y Crónica, Instituto de Salud Carlos III, Madrid, PC, Spain.
Vidal-Sanz M
Experimental Ophthalmology Laboratory, Dept. of Ophthalmology, College of Medicine, University of Murcia, Regional Campus of International Excellence "Campus Mare Nostrum", Murcia Institute of Bio-Health Research (IMIB), E-30100 Murcia, Spain; Red Española Temática de Investigación Cooperativa en Patología Ocular Prevalente y Crónica, Instituto de Salud Carlos III, Madrid, PC, Spain.
de la Villa P
Department of Systems Biology, University of Alcalá, 28871 Alcalá de Henares, Spain; Red Española Temática de Investigación Cooperativa en Patología Ocular Prevalente y Crónica, Instituto de Salud Carlos III, Madrid, PC, Spain.
Pintor J
Department of Biochemistry and Molecular Biology IV, Faculty of Optics and Optometry, Complutense University of Madrid, c/Arcos de Jalón 118, E-28037 Madrid, Spain; Red Española Temática de Investigación Cooperativa en Patología Ocular Prevalente y Crónica, Instituto de Salud Carlos III, Madrid, PC, Spain. Electronic address: jpintor@ucm.es.

MeSH

AgingAnimalsCell CountDisease Models, AnimalElectroretinographyFemaleGenotyping TechniquesGlaucomaIntraocular PressureMiceMice, Inbred C57BLMice, Inbred DBAMicroscopy, FluorescenceNerve DegenerationNight VisionOptic Nerve DiseasesPolymerase Chain ReactionRetinaRetinal DegenerationRetinal Ganglion CellsTonometry, OcularVisual Acuity

Pub Type(s)

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

Language

eng

PubMed ID

24631335

Citation

Pérez de Lara, María J., et al. "Assessment of Inner Retina Dysfunction and Progressive Ganglion Cell Loss in a Mouse Model of Glaucoma." Experimental Eye Research, vol. 122, 2014, pp. 40-9.
Pérez de Lara MJ, Santano C, Guzmán-Aránguez A, et al. Assessment of inner retina dysfunction and progressive ganglion cell loss in a mouse model of glaucoma. Exp Eye Res. 2014;122:40-9.
Pérez de Lara, M. J., Santano, C., Guzmán-Aránguez, A., Valiente-Soriano, F. J., Avilés-Trigueros, M., Vidal-Sanz, M., de la Villa, P., & Pintor, J. (2014). Assessment of inner retina dysfunction and progressive ganglion cell loss in a mouse model of glaucoma. Experimental Eye Research, 122, 40-9. https://doi.org/10.1016/j.exer.2014.02.022
Pérez de Lara MJ, et al. Assessment of Inner Retina Dysfunction and Progressive Ganglion Cell Loss in a Mouse Model of Glaucoma. Exp Eye Res. 2014;122:40-9. PubMed PMID: 24631335.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of inner retina dysfunction and progressive ganglion cell loss in a mouse model of glaucoma. AU - Pérez de Lara,María J, AU - Santano,Concepción, AU - Guzmán-Aránguez,Ana, AU - Valiente-Soriano,F Javier, AU - Avilés-Trigueros,Marcelino, AU - Vidal-Sanz,Manuel, AU - de la Villa,Pedro, AU - Pintor,Jesús, Y1 - 2014/03/12/ PY - 2013/10/16/received PY - 2014/02/13/revised PY - 2014/02/25/accepted PY - 2014/3/18/entrez PY - 2014/3/19/pubmed PY - 2014/7/19/medline KW - DBA/2J KW - electroretinogram (ERG) KW - fluorogold KW - neuronal degeneration KW - retina KW - retinal ganglion cells (RGC) KW - scotopic threshold response (STR) SP - 40 EP - 9 JF - Experimental eye research JO - Exp Eye Res VL - 122 N2 - The DBA/2J mouse is a model of ocular hypertension and retinal ganglion cell (RGC) degeneration, the main features of which are iris pigment dispersion (IPD) and iris stromal atrophy (ISA). These animals also experience glaucomatous changes, including an increase in intraocular pressure (IOP) beginning at about 9-12 months of age and sectorial RGC death in the retina. The aim of this study was to determine the onset of functional changes exhibited by DBA/2J mice in the inner retina. This was performed by means of electroretinographic recordings (scotopic threshold response, STR) and their correlation with morphological changes (loss of RGCs). To this end, we recorded the scotopic threshold response in control C57BL/6J and in DBA/2J mice at different ages. The RGCs, in both DBA/2J and C57BL/6J animals, were identified at 15 months of age by retrograde tracing with an analogue of fluorogold, hydroxystilbamidine methanesulfonate (OHSt), applied on the superior colliculi. Whole mount retinas were processed to quantify the population of RGCs identified by fluorogold tracing and Brn3a immunodetection, and were counted using image analysis software; an isodensity contour plot was generated for each retina. DBA/2J mice showed a significant reduction in the positive STR (pSTR) amplitudes at 12 months of age, as compared to control C57BL/6J mice of the same age. The pSTR mean amplitude decreased to approximately 27.82% of the values recorded in control mice (p = 0.0058). STR responses decreased in both strains as a result of the natural process of aging, but the decrease was more pronounced in DBA/2J mice. Furthermore, quantification of the total number of RGCs identified by OHSt and Brn3a expression showed a reduced population of RGCs in DBA/2J mice as compared to control mice. Regression analysis revealed significant correlations between the decrease in pSTR and a non-homogeneous reduction in the number of RGCs throughout the retina. Our results indicate the existence of a correlation between retinal function impairment and RGC loss. This functional and morphological analysis allows a reliable assessment of the progression of the disease. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/24631335/Assessment_of_inner_retina_dysfunction_and_progressive_ganglion_cell_loss_in_a_mouse_model_of_glaucoma_ DB - PRIME DP - Unbound Medicine ER -