Microvascular dysfunction is a key pathological mechanism of diabetic retinopathy (DR). In recent years, it has been found that the phenomenon of "metabolic memory" is prevalent in diabetic patients, and diabetic microangiopaplasia cannot be avoided even if patients’ blood glucose is well controlled. Therefore, it is necessary to explore DR from a genetic perspective. miR-126 is the unique microRNA specifically expressed in vascular endothelial cells, which is closely related to the formation of neovascularization and can affect the stability of DR microvessels as well as the germination and migration of endothelial cells, and its gene level is significantly negatively correlated with the expression of vascular endothelial cell growth factor. The potential value of intracellular and circulating miR-126 in the regulation of DR microvascular homeostasis, early diagnosis and treatment, and monitoring of disease course has attracted great attention. However, studies in this area are mostly hypothesis-driven and still have some limitations. It is believed that with the rapid development of genomics, the miRNA spectrum and its molecular mechanism in eye development and eye diseases will gradually become clear, which may lead to a breakthrough in the intervention of individual refractory retinal diseases and establish a new miRNA diagnosis and treatment method in the future.
Diabetes retinopathy (DR) is a blinding ocular complication of diabetes, and its pathological mechanism is complex. The damage to the retinal neurovascular unit (NVU) and the imbalance of its coupling mechanism are important pathological foundations. Autophagy plays an important role in the progression of DR. Oxidative stress, endoplasmic reticulum stress, hypoxia, and competitive endogenous RNA regulatory networks can affect the occurrence of autophagy, and autophagy induced cell death is crucial in NVU dysfunction. Retinal neurocyte are non- renewable cells, and adaptive autophagy targeting neuronal cells may provide a new direction for early vision rescue in patients with DR. It is necessary that exploring the possible autophagy interrelationships between ganglion cells, glial cells, and vascular constituent cells, searching for targeted specific cell autophagy inhibitors or activators, and exploring the impact of autophagy on the NVU complex more comprehensively at the overall level. Adopting different autophagy intervention methods at different stages of DR may be one promising research directions for future DR.
Diabetic retinopathy (DR) is one of the main cause of severe visual impairment in diabetic patients. Most of the existing treatments are aimed at patients with intermediate and advanced stages of vision impairment, and are invasive treatments with limited effects. Therefore, it is urgent for non-invasive new therapies and new targets to prevent the risk of DR or delay the progress of DR. Early optimization of metabolic therapies, which are strict control of blood glucose, blood pressure and blood lipid in the early stage of diabetes, may prevent or improve potential and reversible microangiopathy, however, there is still a lack of comprehensive and effective drug targeted therapy and unified clinical application standards. Therefore, this study summarizes the application of new hypoglycemic drugs and some antihypertensive and lipid-lowering drugs in the prevention and treatment of DR in recent years, in order to provide some reference for the clinical early prevention and treatment of this disease.
ObjectiveTo establish a rat model of diabetic microangiopathopathy and simulate the biochemical and pathological changes of diabetic retinal and renal microangiopathopathy. MethodsForty healthy male Sprague-Dawley rats were randomly divided into blank group and model group (10 and 30 rats, respectively). After the rats in blank group and model group were fed ordinary diet and high-fat and high-sugar diet for 5 weeks, respectively, the rats in model group were injected with 1% streptozotocin (STZ) through the abdominal cavity at the dose of 35 mg/kg to establish a type 2 diabetes model. After modeling, the rats were continuously fed until the 10th week (4 weeks after modeling), the general conditions of the rats were observed, and samples were collected for follow-up experiments. Serum creatinine (CREA), triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), microalbuminuria, urinary creatinine (UCr) and urine sugar were detected. Calculate the kidney index and microalbumin/urinary creatinine ratio (UACR). Optical coherence tomography angiography (OCTA) was used to observe the vascular changes and non-perfusion area of retinal superficial capillary plexus. The morphological and structural changes of kidney and retina were observed by hematoxylin-eosin and periodate Scheff staining. The expression of nerve fibers and nucleus of Müller cells in rat retina was observed by immunofluorescence staining. Ultrastructural results of retina were observed by transmission electron microscope. Independent sample t test was used for comparison between groups. ResultsFour weeks after modeling, compared with blank group, the body weight of rats in model group was significantly decreased, and random glucose was significantly increased, with statistical significance (t=5.755, －51.291; P＜0.05). Renal index, urinary glucose and UACR were significantly increased, while UCr was significantly decreased, with statistical significance (t=10.878, 137.273, 3.482, －6.110; P＜0.05). CREA decreased, TG, TC, HDL-C, LDL-C increased, and the differences were statistically significant (t=－28.012, 33.018, 118.018, 13.585, 16.480; P＜0.05). OCTA examination showed that there was no perfusion area of shallow retinal capillaries. The optical microscope showed that the inner boundary membrane of retina in model group was swollen and thickened, the surface was uneven, the inner and outer nuclear layer cells were disordered and the density decreased. Glomerular congestion was accompanied by cortical tubular epithelial swelling, widening of the mesangial area, and thickening of the basement membrane. The results of immunostaining showed that the inner and outer plexiform layers of the retina showed lamellar strong green fluorescence expression, and the inner and outer nuclear layers showed scattered dot green fluorescence expression. Transmission electron microscopy showed that the basal membrane of retinal microvessels in model group was slightly thickened, vascular endothelial cells edema, endothelial nucleus and perinucleus contraction, nuclear membrane contraction, mild mitochondrial swelling, vacuolation. ConclusionHigh-glucose and high-fat feeding plus a single intraperitoneal injection of STZ 35 mg/kg can successfully establish a microangiopathic model of type 2 diabetes.