The Characteristics And Pathogenesis Of Retina In OLETF Rats In The Course Of The Disease Of Diabetic Nephropathy

Objective:Diabetic nephropathy(DN) and Diabetic retinopathy(DR) are both the common chronic microvascular complications of diabetes mellitus(DM). DN has become the major cause of end-stage renal disease(ESRD). And there is a lack of effective treatment and the exact mechanism has not been clarified. And DR is also one of the most important reasons of adults blinding currently. Though the pathogenesis of DN and DR are not entirely clear, but the conventional points of high blood sugar and the formation of abnormal metabolic products leading to the pathological basis of the blood vessel damage were recognized. In theory, they should be parallel development. Although most studies agree that the pathogenesis of DN is related to DR, but not entirely parallel in clinic.Clinical studies have found that before the diagnosis of DM or at the same time, some patients already have the clinical manifestations of kidney damage like proteinuria. Animal experiments have also found that in pre-diabetes, kidney has varying degrees of structural change. So in this study, We observe the characteristics and pathogenesis of retina in OLETF rats in the course of the disease of Diabetic nephropathy and aim to explore the characteristics and possible mechanism and examine whether there are good correlations between DN and DR, and provide reference for early clinical diagnosis and treatment of diabetes complications.Methods: 1) 45 clean grade male OLETF rats and 30 LETO rats were raised in specific pathogen-free conditions, LETO rats were the control group.2) Weekly measured the weight and fasting blood glucose(FBG). Biochemistry method was used to test some biochemical indexes, such as 24 hours urinary microalbuminuria(24h UMA), blood urea nitrogen(BUN) and so on. Oral glucose tolerance test(OGTT) had been done every 4 weeks. IGT was defined as after glucose load, peak plasma glucose>16.8mmol/L or 120min>11.1mmol/L, while DM must had both of them. After 24 h UMA had statistical significance in these two groups, OLETF rats were in DN stage.3) Killed 6 rats in each group in NGT, IGT, DM and DN stage. Used both optical microscope and transmission electron microscopy to observe the retina pathology changes.Results: 1) OGTT results: Compared with the LETO rats, each OLETF rat's blood glucose was normal in 8 weeks, which meets the standard of NGT. In 30 weeks OLETF rats, whose peak plasma glucose was 18.25�4.08 mmol/L and 120 min glucose was 9.56�2.06 mmol/L, which meets the standard of IGT. In 56 and 65 weeks, OLETF rats' blood glucoses were all higher than the LETO rats, and the peak plasma glucoses and 120 min glucoses are both meet the standard of DM.2) Urine protein: There were no statistical differences in 24 h UMA between the NGT stage of OLETF rats and their compared LETO rats. In IGT and DM stage, 24 h UMA began to increase, but still had no statistical differences. Until the DN stage, 24 h UMA in OLETF rats were greater than the LETO rats(P<0.05).3) H&E staining results of OLETF rat retina: OLETF rats in NGT stage had no significant changes with the control group, in IGT stage the ganglion cell layer interstitial edema, and the boundary film surface is not smooth, and the number of ganglion cells were decreased, in DM stage the retina inner and outer nuclear layers were also appear edema, and the ganglion cells decreased significantly, in DN stage the new blood vessels broke through the boundary film of the retina could be observed.4) Electron microscope results of OLETF rats' retina: in NGT stage there were no obvious changes in retina with the control group, in IGT stage the kernel layer cell edema could be observed, ganglion cells mitochondria swelling and cristae vague, cavitation and the retina outer core layer cells arranged in irregular, the retina film plate blurring, fracture. In DM stage kernel layer cell chromatin distribution, cell edema, cytoplasmic appear cavity, ganglion cell layer ganglion cell mitochondria swelling, organelles decreases, cytoplasmic vacuoles degeneration, in DN the retina structural in each layer further damaged.Conclusion: 1) The model of the type 2 DM and type 2 DN were replicated successfully. The OLETF rats' 24 h UMA and the renal morphological changes were consistent with the characteristics of human type 2 DN.2) In each stage of diabetic nephropathy, the pathology morphologic feature of OLETF rats' retinal structure was different, and along with the progression of the course, its organizational structure damage increased gradually, and early damage was mainly in the inner retina, especially the ganglion cell layer.3) The retinal morphological changes could be observed in the early stage of OLETF rats.4) The abnormal of metabolic pathway under high blood sugar, which further leading to the retinal tissue inflammation and ischemia, hypoxia, and participating in the occurrence of DR.5) The damage of blood-retinal barrier was also participated in the occurrence of DR.