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Jennifer C. Lau, Robert A. Linsenmeier, Joseph R. Moskal, Roger A. Kroes; Neural And Vascular Gene Expression Changes In The Diabetic Rat Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5769.
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To investigate changes in mRNA levels of VEGFA, the VEGF receptors Flt1 and Kdr, erythropoietin, ionotropic glutamate receptors, and glutamate transporters in the rat retina as diabetes progresses.
Diabetes was induced in Long-Evans rats with streptozotocin (65mg/kg). Rats with blood glucose >300mg/dl were deemed diabetic. Age-matched controls received buffer only. At 4 and 12 weeks after induction of diabetes, retinas were dissected and mRNA was extracted. Gene expression was analyzed using qRT-PCR. Statistical significance was determined using 2x2 ANOVA followed by post-hoc analysis using Fisher’s PLSD.
Diabetes did not change the retinal mRNA levels of VEGFA and its receptors at the time points studied, although VEGFA protein levels increased after 4 weeks. Erythropoietin mRNA significantly increased at both time points. Diabetes decreased mRNA expression of several genes after 12 weeks, including three glutamate transporters and a majority of subunits within the three classes of ionotropic glutamate receptors: NMDA, AMPA, and kainate. The table summarizes the results of this study.
Diabetes caused more changes in the expression of neurotransmitter-related genes than those related to VEGF. Also, more genes had altered expression after 12 weeks of diabetes than after 4 weeks. Most genes with decreased mRNA levels after 12 weeks are expressed by retinal ganglion cells, which include glutamate transporters and iontropic glutamate receptors. Two genes expressed by retinal ganglion cells but unrelated to glutamate neurotransmission, SNCG and ADORA1, also had decreased mRNA expression after 12 weeks. These findings may indicate ganglion cells were lost as diabetes progressed in the retina. Decreased expression of the glutamate transporter SLC1A3 suggests that Müller cells were also affected. These results show that diabetes not only injures the retinal vasculature, but also affects glutamate signaling in the retina.
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