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  • Keywords Diabetes, angiostatin, VEGF, bFGF, angiogenesis, retinopathy, cytokine, growth factors, photocoagulation, retina.  (1)
  • SHR  (1)
  • 1
    ISSN: 1432-0428
    Keywords: Diabetic retinopathy ; rat model ; hypertension ; SHR ; aminoguanidine ; glycation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Arterial hypertension has been identified as a major secondary risk factor for diabetic retinopathy. However, the mechanisms by which hypertension worsens retinopathy are unknown. Inhibition of advanced glycation product formation prevents the development of experimental diabetic retinopathy in normotensive diabetic rats. In this study the effect of hypertension on the rate of diabetic retinopathy development and the formation of arteriolar thrombosis was evaluated. We also evaluated the effect of aminoguanidine, an inhibitor of advanced glycation end product formation on retinal pathology of diabetic hypertensive rats. After 26 weeks of diabetes, hypertension accelerated the development of retinopathy despite a lower mean blood glucose level than in the non-hypertensive group (diabetic spontaneous hypertensive rats (SHR) 16.00±6.83 mmol/l; diabetic normotensive Wistar Kyoto rats (WKY) 34.9±3.64 mmol/l; p〈0.0001). Diabetic SHR had nearly twice as many acellular capillaries as diabetic WKY (SHR diabetic: 91.9±7.5 acellular capillaries per mm2 of retinal area vs WKY diabetic: 53.7±8.5 acellular capillaries per mm2 of retinal area), and a 3.8-fold increase in the number of arteriolar microthromboses (SHR diabetic 23504±5523 μm2 vs SHR non-diabetic 6228±2707 μm2). Aminoguanidine treatment of SHR diabetic rats reduced the number of acellular capillaries by 50%, and completely prevented both arteriolar deposition of PAS-positive material and abnormal microthrombus formation. These data suggest that hypertension-induced deposition of glycated proteins in the retinal vasculature plays a central role in the acceleration of diabetic retinopathy by hypertension.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Diabetes, angiostatin, VEGF, bFGF, angiogenesis, retinopathy, cytokine, growth factors, photocoagulation, retina.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Proliferative diabetic retinopathy is a major debilitating disease causing most cases of blindness in humans in the Western world. Photocoagulation is the established therapy of proliferative diabetic retinopathy, although the molecular mechanisms of its effects are still not known. Recently angiostatin has been characterized as a potent inhibitor of neovascularization. Apart from a possible down-regulation of angiogenic cytokines, release of angiostatin could initiate the anti-angiogenic effects of retinal photocoagulation.¶Methods. We investigated the regulation of angiostatin and the angiogenic cytokines vascular endothelial growth factor and basic fibroblast growth factor in vivo by comparing vitreal concentrations of 18 control patients and 34 patients with proliferative diabetic retinopathy with and without previous photocoagulation. Concentrations of basic fibroblast growth factor and angiostatin were additionally measured in serum, while vascular endothelial growth factor is known to be regulated locally in the eye. Cytokines were measured by immunological methods.¶Results. Angiostatin could be detected in 2 out of 18 control patients and in 25 out of 34 diabetic patients (p 〈 0.00 001). Most importantly, production of angiostatin in human vitreous correlated significantly with previous retinal photocoagulation (p 〈 0.0001) in patients with proliferative diabetic retinopathy. Only two patients (one control and one diabetic) had detectable serum concentrations of angiostatin. Additionally patients with proliferative diabetic retinopathy and with previous photocoagulation had significantly lower concentrations of vascular endothelial growth factor (0.9 ± 0.1 ng/ml; p 〈 0.0001) than diabetic patients without previous photocoagulation (4.0 ± 0.8 ng/ml). The investigation of vitreal and serum basic fibroblast growth factor concentrations yielded no significant differences between the groups.¶Conclusion/interpretation. Angiostatin is not a regularly expressed angiogenesis inhibitor in human vitreous. The alterations we observed suggest that local release of angiostatin and down-regulation of vascular endothelial growth factor mediate the therapeutic effects of retinal photocoagulation in proliferative diabetic retinopathy. [Diabetologia (2000) 43: 1404–1407]
    Type of Medium: Electronic Resource
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