Research Report Diabetes changes ionotropic glutamate receptor subunit expression level in the human retina Ana R. Santiago a , John M. Hughes b,c , Willem Kamphuis d , Reinier O. Schlingemann b,c , António F. Ambrósio a,e, ⁎ a Center for Neuroscience and Cell Biology, Department of Zoology, University of Coimbra, Coimbra, Portugal b Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands c Ocular Angiogenesis Group, Department of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands d Netherlands Institute for Neuroscience (NIN)-KNAW, an institute of the Royal Netherlands Academy of Arts and Sciences, Department of Cellular Quality Control, Amsterdam, The Netherlands e Center of Ophthalmology of Coimbra, Institute of Biomedical Research on Light and Image (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal ARTICLE INFO ABSTRACT Article history: Accepted 12 December 2007 Available online 6 February 2008 Early diabetic retinopathy is characterized by changes in subtle visual functions such as contrast sensitivity and dark adaptation. The outcome of several studies suggests that glutamate is involved in retinal neurodegeneration during diabetes. We hypothesized that the protein levels of ionotropic glutamate receptor subunits are altered in the retina during diabetes. Therefore, we investigated whether human diabetic patients have altered immunoreactivity of ionotropic glutamate receptor subunits in the retina. In total, 12 donor eyes from subjects with diabetes mellitus were examined and compared to 6 eyes from non-diabetic subjects without known ocular disease, serving as controls. Immunohistochemical analysis was performed using specific antibodies directed against the ionotropic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor subunits GluR1, GluR2, GluR4, and against the N-methyl-D-aspartate glutamate receptor subunit NR1. In the inner plexiform and outer plexiform layers the immunoreactivity of GluR2 and NR1 subunits was significantly increased in subjects with diabetes when compared to the levels found in controls. No significant changes in GluR1 and GluR4 subunit expression were observed. These results suggest that early visual dysfunction in diabetic patients may be due, at least partially, to changes in glutamate receptor subunit expression or distribution. © 2007 Elsevier B.V. All rights reserved. Keywords: Diabetes Human Diabetic retinopathy Ionotropic glutamate receptors 1. Introduction Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults in developed countries. The vascular changes that occur in DR are well documented, and include loss of pericytes and endothelial cells, the formation of microaneu- rysms, basement membrane thickening and blood-retinal barrier breakdown (Cai and Boulton, 2002). In addition to the vascular BRAIN RESEARCH 1198 (2008) 153 – 159 ⁎ Corresponding author. Center of Ophthalmology of Coimbra, IBILI, Faculty of Medicine, Celas, 3000-548 Coimbra, Portugal. Fax: +351 239 480 280. E-mail address: fambrosio@ibili.uc.pt (A.F. Ambrósio). 0006-8993/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2007.12.030 available at www.sciencedirect.com www.elsevier.com/locate/brainres