Alteration of the Blood-Retinal Barrier in Experimental Diabetes Mellitus

Waltman, Stephen R.; Krupin, Theodore; Hanish, Sid; Oestrich, Charles; Becker, Bernard

doi:10.1001/archopht.1978.03910050480018

Cited by 87 publications

(16 citation statements)

References 3 publications

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“…The increased number of retinal vessels leaking IgG in the AR ϩ/ϩ db/db mice indicates breakdown of the blood- retinal barrier, a common sign of diabetic retinopathy in humans (35) and rats (36). AR deficiency prevented this blood-retinal barrier breakdown, indicating that AR contributes to the maintenance of the blood-retinal barrier.…”

Section: Discussionsupporting

confidence: 38%

Aldose Reductase Deficiency Prevents Diabetes-Induced Blood-Retinal Barrier Breakdown, Apoptosis, and Glial Reactivation in the Retina of db/db Mice

et al. 2005

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In 15-month-old db/db mice, signs of diabetic retinopathy, including blood-retinal barrier breakdown, loss of pericytes, neuro-retinal apoptosis, glial reactivation, and proliferation of blood vessels, were evident. These changes in the diabetic retina were associated with increased expression of aldose reductase (AR). To further understand the role of AR in the pathogenesis of diabetic retinopathy, we generated db/db mice with an AR null mutation (AR ؊/؊ db/db). AR deficiency led to fewer retinal blood vessels with IgG leakage, suggesting that AR may contribute to blood-retinal barrier breakdown. AR deficiency also prevented diabetes-induced reduction of platelet/endothelial cell adhesion molecule-1 expression and increased expression of vascular endothelial growth factor, which may have contributed to blood-retinal barrier breakdown. In addition, long-term diabetes-induced neuro-retinal stress and apoptosis and proliferation of blood vessels were less prominent in AR ؊/؊ db/db mice. These findings indicate that AR is responsible for the early events in the pathogenesis of diabetic retinopathy, leading to a cascade of retinal lesions, including blood-retinal barrier breakdown, loss of pericytes, neuro-retinal apoptosis, glial reactivation, and neovascularization. Diabetes 54:3119 -3125, 2005

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Section: Discussionsupporting

confidence: 38%

Aldose Reductase Deficiency Prevents Diabetes-Induced Blood-Retinal Barrier Breakdown, Apoptosis, and Glial Reactivation in the Retina of db/db Mice

et al. 2005

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“…12 The efficacy of insulin treatment in the STZ rat model has been established for many years. In the STZ rat model, insulin treatment has been previously shown to be effective in traditional endpoint analyses of retinal vascular defects 35,36 and retinal neuronal apoptosis 30,37,38 with diabetes. On the basis of these findings, insulin was used as a positive pharmacotherapeutic control to show the ability of the biomarker panel to respond to an effective therapy.…”

Section: Discussionmentioning

confidence: 43%

A multistep validation process of biomarkers for preclinical drug development

et al. 2009

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“…In diabetes, the BRB breaks down and becomes highly permeable before retinopathy is detected by ophthalmoscopy and fluorescein angiography. 22,23,[38][39][40][41][42] For these reasons BRB breakdown is though to be important for clarifying the pathogenesis of diabetic retinopathy. In this study, we demonstrated that intravitreal injection of H 2 O 2 induced higher BRB permeability.…”

Section: Discussionmentioning

confidence: 45%