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Zsolt Ablonczy, Danielle Desjardins, Mohammad Dahrouj, Yueying Liu, Kumar Sambamurti, Shahid Husain, Craig E Crosson; RPE barrier dsyfunction is an early complication in the diabetic eye. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1048.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetes-associated vision loss is often attributed to edema within the layers of the neurosensory retina. The accumulated fluid is commonly thought to be a consequence of leaking neovasular inner retina vessels. However, one of the key functions of the retinal pigment epithelium (RPE) is to actively remove fluid from the retina to keep it relatively dehydrated. Here we investigated the ability of the RPE to resorb fluid in a diabetic rat model.
Diabetes was induced in Brown-Norway rats by means of intraperitoneal injections of streptozotocin (STZ, 65 mg/kg in citrate buffer). Glucose, weight, optical coherence tomographs (OCTs), fluorescence angiography, and electroretinography were performed before STZ treatment and at 1, 4, and 8 weeks post-injection. Glucose readings over 250 mg/dL were considered diabetic. Fluid resorption was monitored following the injection of subretinal saline (1 μL) with the blebs imaged using OCT for 1 hour. For each blebs placed, volume was plotted against time and a linear curve fit determined the rate of fluid resorption.
In STZ-injected animals, blood glucose reached sable levels of 390±50 mg/dL within 72 hours post injection. Sham injected controls had normal (110±25 mg/dL) blood sugar. ERG c-waves began declining at 1 week post injection and continued to decline until 8 weeks. 4 weeks post STZ treatment, fluid resorption by the RPE was decreased (5.6±1.2 µl/cm2*h) compared to sham injected controls (6.5±1.5 µl/cm2*h) and this reduction in RPE fluid transport was significant (3.0±1.6 µl/cm2*h vs. 8.3±0.7 µl/cm2*h) by 8 weeks. However, retina thickness (by OCT) was not altered and vascular features typical of diabetic retinopathy were not detected at any time points.
These studies provided evidence that the ability of the RPE to remove fluid from the extracellular environment in the neural retina can decline rapidly following the onset of hyperglycemia before typical vascular changes are observed. This reduced resorption ability is likely to be a key factor in the accumulation of fluid within the layers of the retina. Pharmacological inhibitors of this dramatic early decrease in RPE fluid transport are expected to be beneficial to prevent the development of edematous fluid in the retina.
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