Diabetes Changes the Levels of Ionotropic Glutamate Receptors in the Rat Retina

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2009 Aug 21

PMID 19693289

Citations 33

Authors

Ana R Santiago

Joana M Gaspar

Filipa I Baptista

Armando J Cristovao

Paulo F Santos

Willem Kamphuis

Antonio F Ambrosio

Affiliations

Soon will be listed here.

Abstract

Purpose: Diabetic retinopathy (DR) is a leading cause of vision loss and blindness among adults between the age 20 to 74. Changes in ionotropic glutamate receptor subunit composition can affect retinal glutamatergic neurotransmission and, therefore, contribute to visual impairment. The purpose of this study was to investigate whether diabetes leads to changes in ionotropic glutamate receptor subunit expression at the protein and mRNA level in the rat retina.

Methods: Changes in the expression of ionotropic glutamate receptor subunits were investigated at the mRNA and protein levels in retinas of streptozotocin (STZ)-induced diabetic and age-matched control rats. Animals were euthanized one, four and 12 weeks after the onset of diabetes. Retinal protein extracts were prepared, and the receptor subunit levels were assessed by western blotting. Transcript levels were assessed by real-time quantitative PCR.

Results: Transcript levels of most ionotropic glutamate receptor subunits were not significantly changed in the retinas of diabetic rats, as compared to age-matched controls but protein levels of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA), kainate, and N-methyl-D-aspartic acid receptors (NMDA) receptors were found to be altered.

Conclusions: The results provide evidence that diabetes affects the retinal content of ionotropic glutamate receptor subunits at the protein level. The possible implications of these changes on retinal physiology and visual impairment in DR are discussed.

Citing Articles

Investigation of the Effects of a Novel NOX2 Inhibitor, GLX7013170, against Glutamate Excitotoxicity and Diabetes Insults in the Retina.

Dionysopoulou S, Wikstrom P, Walum E, Georgakis S, Thermos K Pharmaceuticals (Basel). 2024; 17(3).

PMID: 38543179 PMC: 10974250. DOI: 10.3390/ph17030393.

Untargeted Multiomics Approach Coupling Lipidomics and Metabolomics Profiling Reveals New Insights in Diabetic Retinopathy.

Ancel P, Martin J, Doukbi E, Houssays M, Gascon P, Righini M Int J Mol Sci. 2023; 24(15).

PMID: 37569425 PMC: 10418671. DOI: 10.3390/ijms241512053.

Expression of GABA, GABA, and mGluR2 receptors in the lateral geniculate body of male neonates born to diabetic rats.

Alipour N, Fallahnezhad S, Bagheri J, Babaloo H, Tahmasebi F, Sazegar G Iran J Basic Med Sci. 2023; 26(7):805-811.

PMID: 37396950 PMC: 10311974. DOI: 10.22038/IJBMS.2023.69668.15171.

Visual Dysfunction in Diabetes.

Eggers E Annu Rev Vis Sci. 2023; 9:91-109.

PMID: 37164027 PMC: 11262130. DOI: 10.1146/annurev-vision-111022-123810.

Contrast Increment and Decrement Processing in Individuals With and Without Diabetes.

Tang V, Symons R, Fourlanos S, Guest D, McKendrick A Invest Ophthalmol Vis Sci. 2023; 64(4):26.

PMID: 37083950 PMC: 10132322. DOI: 10.1167/iovs.64.4.26.

References

Gagne J, Milot M, Gelinas S, Lahsaini A, Trudeau F, Martinoli M . Binding properties of glutamate receptors in streptozotocin-induced diabetes in rats. Diabetes. 1997; 46(5):841-6. DOI: 10.2337/diabetes.46.5.841. View

Daley M, Watzke R, Riddle M . Early loss of blue-sensitive color vision in patients with type I diabetes. Diabetes Care. 1987; 10(6):777-81. DOI: 10.2337/diacare.10.6.777. View

Seeburg P . The TINS/TiPS Lecture. The molecular biology of mammalian glutamate receptor channels. Trends Neurosci. 1993; 16(9):359-65. DOI: 10.1016/0166-2236(93)90093-2. View

Jensen J, Schousboe A, Pickering D . Development of calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in cultured neocortical neurons visualized by cobalt staining. J Neurosci Res. 1998; 54(2):273-81. DOI: 10.1002/(SICI)1097-4547(19981015)54:2<273::AID-JNR15>3.0.CO;2-5. View

Lambolez B, Ropert N, Perrais D, Rossier J, HESTRIN S . Correlation between kinetics and RNA splicing of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in neocortical neurons. Proc Natl Acad Sci U S A. 1996; 93(5):1797-802. PMC: 39861. DOI: 10.1073/pnas.93.5.1797. View

Ozawa S, Kamiya H, Tsuzuki K . Glutamate receptors in the mammalian central nervous system. Prog Neurobiol. 1998; 54(5):581-618. DOI: 10.1016/s0301-0082(97)00085-3. View

Vandenbranden C, Kamphuis W, Nunes Cardozo B, Kamermans M . Expression and localization of ionotropic glutamate receptor subunits in the goldfish retina--an in situ hybridization and immunocytochemical study. J Neurocytol. 2001; 29(10):729-42. DOI: 10.1023/a:1010938420762. View

Ambati J, Chalam K, Chawla D, DAngio C, Guillet E, Rose S . Elevated gamma-aminobutyric acid, glutamate, and vascular endothelial growth factor levels in the vitreous of patients with proliferative diabetic retinopathy. Arch Ophthalmol. 1997; 115(9):1161-6. DOI: 10.1001/archopht.1997.01100160331011. View

Thoreson W, Witkovsky P . Glutamate receptors and circuits in the vertebrate retina. Prog Retin Eye Res. 1999; 18(6):765-810. DOI: 10.1016/s1350-9462(98)00031-7. View

10.

Barber A, Antonetti D, Kern T, Reiter C, Soans R, Krady J . The Ins2Akita mouse as a model of early retinal complications in diabetes. Invest Ophthalmol Vis Sci. 2005; 46(6):2210-8. DOI: 10.1167/iovs.04-1340. View

11.

Parisi V, Uccioli L . Visual electrophysiological responses in persons with type 1 diabetes. Diabetes Metab Res Rev. 2001; 17(1):12-8. DOI: 10.1002/dmrr.177. View

12.

Dijk F, Kraal-Muller E, Kamphuis W . Ischemia-induced changes of AMPA-type glutamate receptor subunit expression pattern in the rat retina: a real-time quantitative PCR study. Invest Ophthalmol Vis Sci. 2003; 45(1):330-41. DOI: 10.1167/iovs.03-0285. View

13.

Sokol S, Moskowitz A, Skarf B, Evans R, Molitch M, Senior B . Contrast sensitivity in diabetics with and without background retinopathy. Arch Ophthalmol. 1985; 103(1):51-4. DOI: 10.1001/archopht.1985.01050010055018. View

14.

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A . Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3(7):RESEARCH0034. PMC: 126239. DOI: 10.1186/gb-2002-3-7-research0034. View

15.

Dev K, Nishimune A, Henley J, Nakanishi S . The protein kinase C alpha binding protein PICK1 interacts with short but not long form alternative splice variants of AMPA receptor subunits. Neuropharmacology. 1999; 38(5):635-44. DOI: 10.1016/s0028-3908(98)00230-5. View

16.

Delibas N, Kilinc I, Yonden Z, Sutcu R, Gultekin F, Koylu H . NMDA receptor subunits 2A and 2B decrease and lipid peroxidation increase in the hippocampus of streptozotocin-diabetic rats: effects of insulin and gliclazide treatments. Int J Neurosci. 2004; 114(3):391-401. DOI: 10.1080/00207450490270893. View

17.

Li N, Young M, Bailey C, Smith M . NMDA and AMPA glutamate receptor subtypes in the thoracic spinal cord in lean and obese-diabetic ob/ob mice. Brain Res. 1999; 849(1-2):34-44. DOI: 10.1016/s0006-8993(99)02070-3. View

18.

Sucher N, Akbarian S, Chi C, Leclerc C, Awobuluyi M, Deitcher D . Developmental and regional expression pattern of a novel NMDA receptor-like subunit (NMDAR-L) in the rodent brain. J Neurosci. 1995; 15(10):6509-20. PMC: 6578025. View

19.

Trudeau F, Gagnon S, Massicotte G . Hippocampal synaptic plasticity and glutamate receptor regulation: influences of diabetes mellitus. Eur J Pharmacol. 2004; 490(1-3):177-86. DOI: 10.1016/j.ejphar.2004.02.055. View

20.

Kowluru R, ENGERMAN R, Case G, Kern T . Retinal glutamate in diabetes and effect of antioxidants. Neurochem Int. 2001; 38(5):385-90. DOI: 10.1016/s0197-0186(00)00112-1. View