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J. Zhang, G. Xu, Y. Jin, S.H. Sinclair, Y. Luo, Y. Li, W. Li; Diabetic Neuronopathy and the Early Breakdown of Blood–Retinal Barrier (BRB) . Invest. Ophthalmol. Vis. Sci. 2005;46(13):445.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine factor(s) contributing to the early breakdown of BRB in diabetes. Methods: Male Sprague–Dawley rats were used to establish diabetic animals by a single intraperitoneal injection of streptozotocin (60mg/kg). After induction, the diabetic rats were tested and sacrificed at day 0, 1, 4, 7, 10 and 14, respectively. Breakdown of BRB was quantitated by Evans Blue technique: Evans blue (µg)/pooled retinal dry weight (g)________ Time–averaged Evans blue concentration (µg/µl) X circulation time (h) In situ end labeling of DNA terminal dUTP nick end labeling (TUNEL) was simultaneously conducted to allow identification of retinal cell apoptosis in cryo–sections (15 µm). Results: The earliest breakdown of BRB was detected by Evans blue technique (n=6, p<0.01) on day 4 after diabetes induction. From then, the leakage of Evans blue into retina increased rapidly (day 4 to day 10) but then slowed after day 10. TUNEL staining did not demonstrate a significant level of apoptosis in ganglion or inner nuclear layers until day 10. At day 10, 10% ganglion cells (n=6, p< 0.05) and ∼15% cells in the inner nuclear layer (n=6, p<0.01) were TUNEL–positive. Vascular endothelial cells and pericytes did not demonstrate staining by TUNEL on retinal cross sections at any of the times studied. Conclusions: Breakdown of BRB began early after induction of diabetes and appeared to be a functional alteration because vascular cell injury (both endothelial cell and pericyte) that was sufficient to result in apoptotic staining was not detected at this stage. Retinal neuron death, however, was associated with BRB breakdown, although not at the earliest detected times. The co–existence of functional breakdown of BRB and pre–morphological stage of neuronopathy suggests common injury pathways leading to subsequent retinal cell apoptosis in both neuron and vascular cell populations.
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