Epigenetic modifications such as DNA methylation, histone post-translational modifications, non-coding RNA are reversible, heritable alterations which are induced by environmental stimuli. Major risk factors of diabetes and diabetic complications including hyperglycemia, oxidative stress and advanced glycation end products, can lead to abnormal epigenetic modifications in retinal vascular endothelial cells and retinal pigment epithelium cells. Epigenetic mechanisms are involved in the pathogenesis of macular edema and neovascularization of diabetic retinopathy (DR), as well as diabetic metabolic memory. The heritable nature of epigenetic marks also playsakey role in familial diabetes mellitus. Further elucidation of epigenetic mechanisms in DR can open the way for the discovery of novel therapeutic targets to prevent DR progression.
ObjectiveTo investigate the expression of interleukin-18（IL-18）and signal transducers and activators of transcription 5（STAT5）in retina of 4-24-week-old diabetic rats, and explore the potential molecular mechanisms involved in diabetic retinopathy (DR).MethodsRetinal gene expression profile of healthy and 8-week-old diabetic rats was established with restriction fragment differential displaypolymerase chained reaction (RFDD-PCR), and the differences was analyzed by bioinformatics. IL-18 and STAT5 were filtrated as the candidate genes of DR. The expression of IL-18 and STAT5 in retina of diabetic rats with the age of 4, 8, and 24 weeks was observed by semi-quantitative reverse transcriptase-polymerase chain reaction（RT-PCR）.ResultsThe result of RFDD-PCR showed:expression of IL-18 was higher in healthy retina than that in diabetic one; expression of STAT5 was not found in healthy rats but in diabetic ones. The result of RT-PCR showed：compared with the normal, high expression of IL-18 was found in 4-week diabetic retina, reduced in 8-week one, and decreased to the lowest in 24-week one. The expression of STAT5 was not observed in healthy or 4week diabetic retina, but occurred in 8-week one, and increased in 24-week one. ConclusionThe expression of IL-18 and the activation of STAT5 may relate to the occurrance of DR. The expression of IL-18 doesn′t depend on the activation of STAT5. (Chin J Ocul Fundus Dis, 2005,21:258-260)
The prevalence of diabetes mellitus in adults of China has reached 12.8%. Diabetic retinopathy (DR) accounts for approximately 1/4-1/3 of the diabetic population. Several millions of people are estimated suffering the advanced stage of DR, including severe non-proliferative DR (NPDR), proliferative DR (PDR) and diabetic macular edema (DME), which seriously threat to the patients’ vision. On the basis of systematic prevention and control of diabetes and its complications, prevention of the moderate and high-risk NPDR from progressing to the advanced stage is the final efforts to avoid diabetic blindness. The implementation of the DR severity scale is helpful to assess the severity, risk factors for its progression, treatment efficacy and prognosis. In the eyes with vision-threatening DR, early application of biotherapy of anti-vascular endothelial growth factor can improve DR with regression of retinal neovascularization, but whether it is possible to induce capillary re-canalization in the non-perfusion area needs more investigation. Laser photocoagulation remains the mainstay treatment for non-center-involved DME and PDR.
Purpose To clarify the relationship between diabetic retinopathy (DR) and maculopathy (DM) and explore the clinical implication of independent graduation of DM. Methods Fundus fluorescein angiography and routine ophthalmological examination were performed on 582 cases of diabetes.Their ocular fundi and macular impairments were graded. Results In general,the severity of diabetic macular impairment was accompanied by retinal involvement,but discrepancy existed between DM and DR.Degree I DM occurred in 5.4% (16/294) among cases without DR,in stage IV DR,degree Ⅲ DM accounted for the most part ,54.5% (116/213).There were still 5.1% (2/39) cases without DM in stage Ⅴ DR. Conclusion The degree of the macular lesions in DM is often not in parallel with the gradation of general affections in retinal tissue other than in macular region in DR,therefore,independentg radation of diabetic maculopathy has its clinical significance for choosing the optimal period of treating maculopathy and preserving the macular function. (Chin J Ocul Fundus Dis,2000,16:153-154)
To evaluate the tberapeutlc effect of diode laser photocoagulation trearment on eases of diabetic retinopathy with certain degree of refractive media opacity. METHODS: Diode laser photocoagulation treatment were given to 36 selected cases (40 eyes )of diabetic retinopathy who can not be treated with argon laser because of refractive media opacity, Before and after treatment,visual acuity and fundus were examined and fundus fluorescein angiography and retinal color photographp were taken. The follow-up period was 8~14 months (with an average of 11 months) RESULT:Visual acuity were improved or maintained in 29 eyes(about 73%)of the 34 eyes of proliferative diabetic retinopathy ,retinal new vessels partly or entirely regressed in 25 eyes(about 74%). CONCLUTION ;Tbe effect of diode laser treatment on patients with diabetic retinopatby with certain degree of lens/vitreous opacity is relatively safisfactory. （Chin J Ocul Fundus Dis,1996,12:111- 113）
Purpose To observe the color motion perception of patients with diabetic retinopathy (DR) in very early stage and find a good way to diagnose early DR in time． Methods The motion perceptions of patients with early DR and normal subjects were tested by using equiluminant moving chromatic grating and moving luminance grating generated on VGA monitor in a PC compatible computer and the results were compared with those of electroretinogram(ERG),oscillatory potentials(OPs) and color perception． Results When the two gratings were of equal spatial frequency and equal time frequency,the normal subjects judged that chromatic grating moved faster than luminance grating．Very signifincant differences were detected between blue/yellow grating and black/white grating while the luminance contrast of was 80% and the velocity was 20.2 mm/s or 14.3mm/s(Plt;0.01).The abnormal ratio of color motion perception(69.2%)was higher than that of color vision(43.6%) and ERG OPs(48.9%) when the luminance contrast of black/white grating was 80% and the velocity was 20.2mm/s. Conclusion The test of color motion perception provides new method for diagnosing early DR. (Chin J Ocul Fundus Dis,1998,14:135-138)
Objective To determine the affected factors of intraorbital hemodynamic results in diabetic retinopathy (DR) and the risk factors related to the occurrence of DR. Methods Posterior ciliary artery (PCA), central retinal artery (CRA), central retinal vein (CRV), and vortex vein (VV) of 68 patients with DR were measured by color Doppler flow image (CDFI). Thirty-one hemodynamic parameters, including systolic velocity, diastolic velocity, mean velocity, resistive index, pulsatility index and accelerative velocity of ophthalmic artery (OA), and other variates (blood pressure, blood sugar, gender, age, duration of the disease, and so on) were collected and clustered in a principal components analys is following a forward, stepwise logistic regression on these components. Results Nine principal components were extracted from 37 original variates, reflecting the velocity of OA, velocity of PCA, resistance of OA, velocity of CRA,resistance of CRA, resistance of PCA, time-related factor, venous drainage factor and gender factor, respectively. In the result of logistic regression, resistance of OA, velocity of CRA, resistance of PCA, time-related factor, and venous drainage factor were the risk factors related to DR. Conclusion The first risk factor affecting DR is time, and intraorbital hemodynamic abnormity influencing the development of diabetic retinopathy may be the increase of resistance of OA, decrease of velocity of CRA, decrease of resistance of PCA, and increase of venous drainage. (Chin J Ocul Fundus Dis，2004，20：98-100)
Objective To observe the effect of high glucose on the expression of activating transcription factor 4 (ATF4) in cultured retinal Muuml;ller glia cells. Methods The retinal tissue of Sprague-Dawley (SD) rats was collected, and Muuml;ller cells were isolated and cultured. The glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) of Muuml;ller cells were identified by streptavidin-biotin-peroxidase complex. Cultured rat Muuml;ller cells were divided into control group (5.5 mmol/L glucose), group A (20 mmol/L glucose), group B (30 mmol/L glucose) and group C (40 mmol/L glucose). ATF4 protein expressions in Muuml;ller cells of four groups were measured by Western blot four days after cultured. Results GFAP and GS expressed in more than 95% of Muuml;ller cells. Over 95% of Muuml;ller cells of group A, B and C were positive for GFAP and GS. Western blots indicated that ATF4 protein in group A, B and C increased obviously compared with the control group (q=0.293, 0.754,0.484;P＜0.05). Conclusion High glucose can increase the expression of ATF4 protein and cause endoplasmic reticulum stress in retinal Muuml;ller glia cells in vitro.
Diabetic retinopathy (DR) is one of the microvascular complications of diabetes mellitus (DM). Like other macrovascular complications of DM, the development and progression of DR is influenced by a variety of systemic and local factors. It is essential to understand the importance of multidisciplinary collaboration. Systemic risk fators such as hyperglycemia, hypertension, dyslipidemia and diabetic nephropathy should be treated before effective DR management can be implemented. Through multidisciplinary collaboration, we can prevent the development of DR, slow the progression of DR, and improve the safety of perioperative care. Thereby enhancing the level of prevention and control of DM complications, including DR.
Diabetic retinopathy is a serious complication of diabetes and is the leading cause of blindness in people with diabetes. At present, there are many views on the pathogenesis of diabetic retinopathy, including the changes of retinal microenvironment caused by high glucose, the formation of advanced glycation end products, oxidative stress injury, inflammatory reaction and angiogenesis factor. These mechanisms produce a common pathway that leads to retinal degeneration and microvascular injury in the retina. In recent years, cell regeneration therapy plays an increasingly important role in the process of repairing diseases. Different types of stem cells have neurological and vascular protection for the retina, but the focus of the target is different. It has been reported that stem cells can regulate the retinal microenvironment and protect the retinal nerve cells by paracrine production, and can also reduce immune damage through potential immunoregulation, and can also differentiate into damaged cells by regenerative function. Combined with the above characteristics, stem cells show the potential for the repair of diabetic retinopathy, this stem cell-based regenerative therapy for clinical application provides a pre-based evident. However, in the process of stem cell transplantation, homogeneity of stem cells, cell delivery, effective homing and transplantation to damaged tissue is still a problem of cell therapy.