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A. Ly, P. Yee, E. L. Fletcher; Hypoxia Precedes Neuronal Dysfunction in an Animal Model of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4913. doi: https://doi.org/.
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Diabetic retinopathy is the leading cause of blindness in working-aged adults. In addition to vascular abnormalities, there are alterations in neuronal and glial function. This project attempted to characterize the time course of neuronal, glial changes in relation to the development of hypoxia during diabetes.
Sprague-Dawley rats were rendered diabetic by an i.v injection of streptozotocin (50mg/kg). Control rats received injections of citrate buffer alone. Following 1, 4, 6 and 12 weeks of diabetes (N=10-14 per timepoint), retinal function was assessed using the electroretinogram. Retinal hypoxia was assessed using the Hypoxyprobe system; pimonidazole was injected intravitreally. Following 3 hours retinae were fixed in 4% PF and processed for pimonidazole immunocytochemistry. Changes in retinal glia were assessed using immunocytochemistry with GFAP, Connexin-26; blood vessels were labeled with NG2 and isolectin-B4.
Rod photoreceptor and cone post-receptoral losses, were detected following 6 weeks of diabetes. Hypoxyprobe labeling was increased in the inner retina at 4 weeks of disease and specifically labeled the Inner Plexiform Layer, ganglion cells and Müller cells at 6 weeks. Hypoxyprobe labeling of Müller cells colocalised with upregulated GFAP in their processes. At 6 weeks, Connexin 26 immunolabelling revealed the protein was decreased in peripheral diabetic retinae. In flatmounted diabetic retina, Connexin 26 indicated a change in astrocyte morphology.
These data suggest that while glial cell and neuronal anomalies occur concurrently in the retina during diabetes, hypoxia may precede both. Further work will be necessary to determine the precise relationship between glia and the retinal vasculature during diabetes.
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