Hypertension increases retinal inflammation in experimental diabetes: a possible mechanism for aggravation of diabetic retinopathy by hypertension.
Inflammation is pivotal to the pathogenesis of diabetic retinopathy (DR). Hypertension is the main secondary risk factor associated with DR. The mechanisms by which hypertension increases the risk for DR are poorly understood. The aim of the current study was to investigate the contribution of genetic hypertension to early retinal inflammation in experimental diabetes. Diabetes was induced in 4-week-old (developing hypertension) and 12-week-old (fully hypertensive) spontaneously hypertensive rats (SHR) and age-matched control normotensive Wistar Kyoto (WKY) rats by administration of streptozotocin (50 mg/kg, i.v); after 20 days the rats were sacrificed and the retinas were collected. ED1 positive cells, ICAM-1 and VEGF levels were significantly higher in diabetic SHR in both prehypertensive and hypertensive ages (p < 0.005). NF-kappaB p65 levels were higher in prehypertensive SHR and in hypertensive diabetic SHR (p < 0.05). Induction of diabetes in normotensive WKY rats did not show any alteration in retinal expression of inflammatory parameters. Therefore, we conclude that the developing hypertension and also the fully developed hypertension lead to earlier development of inflammation in diabetic retina. Aggravation of the inflammatory process may be involved in the mechanism by which essential hypertension exacerbates retinopathy in the presence of diabetes.
Silva
Kamila C
KC
Renal Pathophysiology Laboratory, Faculty of Medical Sciences, State University of Campinas (Unicamp), Campinas, São Paulo, Brazil.
Pinto
Camila C
CC
Biswas
Subrata K
SK
de Faria
José B Lopes
JB
de Faria
Jacqueline M Lopes
JM
D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000209:etiology* / Q000378:metabolism; D053331:Ectodysplasins / Q000378:metabolism; D006973:Hypertension / Q000150:complications* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012173:Retinitis / Q000209:etiology* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D053331:Ectodysplasins; D051996:Transcription Factor RelA; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D018799:Intercellular Adhesion Molecule-1