Diabetic retinopathy is a vascular complication of diabetes, and homocysteine is an intermediate product of methionine metabolism. Hyperhomocysteinemia can directly or indirectly damage vascular endothelial cells, causing vascular endothelial cells dysfunction and participating in the occurrence and development of diabetic retinopathy. Uric acid is the final product of purine metabolism. Hyperuricemia can cause vascular endothelial dysfunction, oxidative metabolism, platelet adhesion and aggregation dysfunction, thus participating in the occurrence and development of diabetic retinopathy. In recent years, there have been many studies on the correlation between diabetic retinopathy and levels of homocysteine and uric acid. This article reviews the relevant literature at home and abroad in order to provide new information for the prevention and treatment of diabetic retinopathy.
Objective Methods Ninety male Wister rats were randomly divided into normal control group, diabetic group and FTY720 group, thirty rats in each group. Diabetes was induced by giving a single intraperitoneal injection of streptozocin. FTY720 group was administered with FTY720 at a dose of 0.3 mg/kg by oral gavage daily for 3 months after establishment of diabetes. All rats were used for experiments following intervention for 3 months in FTY720 group. Immunohistochemical staining was used to observe the expression and distribution of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1), and the positive cells were counted. Real-time reverse transcription PCR was used to measure mRNA expression of ICAM-1 and VCAM-1. Fluorescein isothiocyanate-Concanavalin A perfusion was used to detect retinal leukocytes adhesion. Evans blue (EB) perfusion was used to analyze retinal vascular permeability. Immunofluorescence staining was used to detect retinal inflammatory cells infiltration. Results In diabetic group, both ICAM-1(t=12.81) and VCAM-1 (t=11.75) positive cells as well as their mRNA expression (t=16.14, 9.59) were increased compared with normal control group, with statistical significance (P < 0.05). In FTY720 group, both ICAM-1(t=-9.93) and VCAM-1 (t=-6.61) positive cells as well as their mRNA expression (t=-15.28, -6.10) were decreased compared with diabetic group, with statistical significance (P < 0.05). Retinal leukocytes adhesion (t=16.32) and EB permeability (t=17.83) were increased in diabetic group compared with normal control group, while they were decreased in FTY720 group compared with diabetic group(t=-9.93, -11.82),with statistical significance (P < 0.05). There were many CD45 positive leukocytes infiltration in retina of diabetic group, including CD11b positive macrophage/activated microglia, while both of them were little in FTY720 group. Conclusions FTY720 can decrease retinal leukocytes adhesion, reduce retinal vascular permeability and inflammatory cells infiltration, which is associated with down-regulation of ICAM-1 and VCAM-1.
The pathogenesis of diabetic retinopathy (DR) is complex and there are many related risk factors. It is related to the course of diabetes, blood glucose, blood pressure, and blood lipids, among which the course of disease and hyperglycemia are recognized main risk factors. In addition, other factors which include heredity, gender, age, obesity, pregnancy, insulin use, can also affect the occurrence and development of DR, but there is no unified conclusion about its correlation. A comprehensive understanding of the risk factors that affect DR can provide new ideas for the prevention, diagnosis, treatment, and intervention of DR.
Microparticles are small vesicles that are released by budding of the plasma membrane during cellular activation and apoptotic cell breakdown. A spectrum of cell types can release microparticles including endothelial cells, platelets, macrophages, lymphocytes and tumor cells. Biological effects of microparticles mainly include procoagulant activity, inhibition of inflammation and cancer progression. The present study shows that vitreous microparticles isolated from proliferative diabetic retinopathy (PDR) stimulated endothelial cell proliferation and increased new vessel formation, promoting the pathological neovascularization in PDR patients. Oxidative stress induces the formation of retina pigment epithelium-derived microparticles carrying membrane complement regulatory proteins, which is associated with drusen formation and age related macular degeneration. Microparticles from lymphocyte (LMP) play an important role in anti-angiogenesis by altering the gene expression pattern of angiogenesis-related factors in macrophages. Besides, LMP are important proapoptotic regulators for retinoblastoma cells through reduction of spleen tyrosine kinase expression and upregulation of the p53-p21 pathway which ultimately activates caspase-3. However, how to apply the microparticles in the prevention and treatment of retinal diseases is a major challenge, because the study of the microparticles in the fundus diseases is still limited. Further studies conducted would certainly enhance the application of microparticles in the fundus diseases.
Objective To observe the expression of p53, bcl-2 genes, vascular endothelial cell growth factor（VEGF）, basic fibroblast growth factor（bFGF）, insulin-like growth factor-I （IGF-I）, and the receptors of these factors of retinal vascular endothelial cells (VECs) of 1- to 20-week diabetic rats, and the relationship between the expressions and cell cycle arrest.Methods Retinal sections of diabetic rats induced by alloxan were immunohistochemically stained and observed by light microscopy (LM) and electron microscopy (EM). Dot blotting and Western blotting were used to determine the expression of mRNA, proteins of p53 and bcl-2. Results Under LM, immunohistochemical positive expression of p53 and bcl-2 were found on the vessels of ganglion cell layer and inner nuclear layer of retinae of 8- to 20-week diabetic rats; under EM, these substances were observed depositing in VECs. The retinal VECs also expressed VEGF, bFGF, IGF-I and their receptors. There was no positive expression of other cell types in these retinae, all cell types of retinae in control group, or all cells of retinae of diabetic rats with the course of disease of 1 to 6 weeks. The result of dot blotting revealed that retinal tissue of 20-week diabetic rat expressed p53 and bcl-2 mRNA, and the result of Western blotting revealed that they also expressed p53 and bcl-2 proteins. But retinal tissues of control group did not. Positive expression of bax was not found in the retinae in control group or 1- to 20-week diabetic rats. Conclusion p53, bcl-2 may introduce cell cycle arrest of VECs of retinae in 8- to 20-week diabetic rats. High glucose might stimulate the expression of VEGF, bFGF, IGF-I and their receptors, and the growth factors may keep VECs surviving by self-secretion. (Chin J Ocul Fundus Dis，2003，19：29-33)
PURPOSE:To investigale the influence of orally administered aldose reduetace inhibitor(ARI) and myo-inositol (MI)for contents of gluecose,sorbitol and myo-inositol in experimental diabetic retinal tissue in rat. METHODS :The STZ-induced diabetic rats were administered ARI or MI by oral. The glucose sorbitol and myo-inositol in retinal tissues were analysed by high performance liquid chromatography after experimental period of 6 montbs. RESULTS:It was found that the contents of glucose and sorhitol were increased and myo inosltol was decreased in diabetic group. In diabetes with ARI group.the content of sorbitol was increased although the glucose was in high level. In diabetes wilb MI group,the sorbitol accumulaled and coment of myo-inositol was close to the normal control group. CONCLUSIONS:The ARI can effectively obstruct sorbitol accumulation in retina. MI increase myo-inositol level but fail to reduce sorbitol contenl of retina. （Chin J Ocul Fundus Dis,1997,13: 75-77 ）
Objective To observe the short-term effect of changing the sequence of PRP and MLP on the pre-proliferative or proliferative diabetic retinopathy patients with clinical significant macular edema (CSEM). Methods Sixty-three consecutive pre-proliferative or proliferative diabetic retinopathy outpatients (103 eyes) with clinical significant macular edema were selected and divided into two groups: 54 eyes in patients of group A accepted MLP one month prior to PRP and 49 eyes in patients of group B accepted the photocoagulative therapies in a contrary sequence. All the patients were followed up for 3 to 13 months and visual acuity. Light sensitivity of 5deg;macular threshold, and FFA were performed pre- and post-photocoagution. Results The improvement of visual acuity was found to be better in group A than that of group B (Plt;0.01) 2 months after the therapy, since then, there was no significant defference (Pgt;0.05) in both groups. Three and 4 months after the treatment, there was no significant difference in change of light sensitivity of 5deg;macular threshold in both groups. The macular leakages of 59 eyes, 32 ingroup A and 27 in group B, were well controlled. Conclusion Among the pre-proliferative or proliferative diabetic retinopathy patients with CSEM, visual acuity of those who accept MLP prior to PRP more rapidly than those who accept contrary sequence of photocoagulation, but the changing of therapeutic sequence might have no dramatic influence on light sensilivity of 5deg;macular threshold. (Chin J Ocul Fundus Dis,2000,16:150-152)