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S.X. Zhang, J. Sima, J. Fant, J. Ma, A. Ottlecz, G.N. Lambrou; Strain-Related Differences in Oxygen- and Diabetes-Induced Retinal Vascular Permeability in Brown-Norway and Sprague-Dawley Rats . Invest. Ophthalmol. Vis. Sci. 2003;44(13):955.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Increased retinal vascular permeability (RVP) is a feature that develops early during the course of diabetic and other ischemic retinopathies. This study was to compare strain-related differences in the RVP of Brown-Norway (BN) and Sprague-Dawley (SD) rats in oxygen-induced retinopathy (OIR) and in streptozotocin (STZ)-induced diabetic retinopathy. Methods: OIR was induced by exposing neonatal rats to hyperoxia (75% O2) from P7 to P12. RVP was measured on days P12, P14, P16, P18, P22, P30, and P36 using the Evans Blue method. Diabetes was induced by STZ (60 mg/kg, i.v.) in adult rats and was monitored by blood glucose levels. RVP was evaluated on days 1, 3, 7, 10, and at 2, 4, 8, and 16 wks after the induction of diabetes. Retinal VEGF levels were assessed by Western blot analysis. Results: In BN-OIR rats, RVP started to increase at P12 with a 3.2-fold elevation compared to age-matched controls (P=0.0003), reaching its peak at P16 with an 8.7-fold increase over the control level (P=7.5E-06). Between P18 and P22, the permeability slowly declined (7.6-fold and 4.2-fold, respectively), reaching the basal level after P30. In SD-OIR rats, RVP began to increase later (P14) and the peak of the hyper-permeability was lower than that in BN rats (2.2-fold over the control). These observations correlated with different retinal VEGF levels in the two strains. In STZ-diabetes BN rats, hyper-permeability occurred 24 h after the STZ injection (1.4-fold increase; P=0.0292) and reached its peak 2 wks after the induction of diabetes with a 1.8-fold elevation as compared to controls (P=0.0074). The hyper-permeability lasted for at least 8 wks (1.9-fold; P=0.0036). In SD rats, RVP started to increase 3 days after the STZ-injection (1.3-fold; P=0.0271) and reached its highest value at 1 wk (1.5-fold; P=0.004), dropping to the control level after 2 wks. Retinal VEGF induction correlated with the differences in vascular permeability, STZ-BN rats exhibited higher levels, than did STZ-SD rats. Conclusions: Both in OIR and in STZ-diabetes, increased RVP is significantly higher and lasts longer in BN than in SD rats. These differences may be due to different retinal VEGF expressions in these two strains. Future studies are warranted to investigate the genetic differences between BN and SD rats that may contribute to their different susceptibility to angiogenesis and retinal edema.
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