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.
Purpose To investigate the effects of intervention with Tanakan on anterior ocular segment in diabetic retinopathy (DR) after retinal photocoagulation． Methods Prospective random controlled study was performed on 72 patients (72 eyes) with ultrasound biomicroscopy (UBM),by obtaining and quantitatively analyzing the changes of anterior ocular segment including anterior chamber, anterior chamber angle, ciliary body and choroids before and the 3rd day and the 7th day after retinal photocoagulation. Results Three days after photocoagulation, significant elev ated IOP and narrowed chamber angle were observed in control group and 4 eyes (1 1.11%) in Tanakan group (Plt;0.01)． Choroidal detachment in 32 eyes (88.89%) in control group and in 2 eyes (5.56%) in Tanakan group and the severity of ciliochoroidal detachment in tanakan group was significantly lower than that in control group． Conclusion Tanakan is effective to prevent the complications of anterior segment, such as ciliochoroidal detachment, elevation of IOP, narrowing of chamber angle occurring early after retinal photocoagulation and reduce the severity of ciliochoroidal detachment． (Chin J Ocul Fundus Dis, 2001,17:187-189)
Circular RNA (circRNA) is a new group of endogenous non-coding RNAs produced by back-splicing, which has multiple molecular functions such as acting as microRNA sponges, regulators of transcription and splicing, adaptors for protein-protein interaction. Recent studies have shown that circRNA play an essential role in development and progression of retinal microvascular dysfunction, diabetic retinopathy, age-related macular degeneration, proliferative vitreoretinopathy, eye diseases caused by hyperhomocysteine and ocular malignancy. In pathological conditions, the differential expression of circRNA alters the transcription and translation of corresponding genes, thus changing the activity and function of cells. CircRNA may become a new marker and prognostic indicator of fundus diseases, and its targeted intervention may also become a potential treatment for fundus diseases.
ObjectiveTo observe the changes in the biomechanical properties of the cornea of diabetic retinopathy (DR), and analyze its relationship with the degree of DR. MethodsA retrospective study. From September 2020 to February 2021, 83 patients with type 2 diabetes (T2DM) combined with DR treated in the Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, 83 eyes (DR group), 30 patients with T2DM without DR recruited from the outpatient clinic 30 eyes (NDR group) and 30 eyes of non-diabetes patients (NDM group) were included in the study. All left eyes were chose as the study eye. Among the 83 eyes in the DR group, 39 eyes were non-proliferative DR (NPDR) and 44 eyes were proliferative DR (PDR). Based on this, they were divided into NPDR group and PDR group. There was no statistically significant difference in age (t=1.10) and sex ratio (χ2=0.46) among patients in the DR group, NDR group, and NDM group (P>0.05); body mass index (t=3.74), glycosylated hemoglobin (t=35.02) and the length of the eye axis (t=5.51), the difference was statistically significant (P<0.05). The eye response analyzer (ORA) was used to measure the corneal hysteresis (CH), corneal resistance factor (CRF), Goldman related intraocular pressure (IOPg), and corneal compensatory intraocular pressure (IOPcc). The corneal topography was used to measure the central corneal thickness (CCT) of the examined eye. The differences of CCT, IOPcc, IOPg, CH, CRF among multiple groups were compared by one-way analysis of variance. Multiple linear regression was used to analyze the relationship between CH, CRF and related influencing factors in DR patients. ResultsThere were statistically significant differences in CCT, IOPcc, IOPg, CH, and CRF among the eyes of the DR group, NDR group, and NDM group (F=3.71, 5.60, 9.72, 9.02, 21.97; P<0.05). Pairwise comparisons were between groups, CH, CRF: the difference between the DR group and the NDM group and the NDR group was statistically significant (P<0.05); CCT: the difference between the DR group and the NDM group was statistically significant (P<0.05), and The difference in the NDR group was not statistically significant (P>0.05). CCT, CH, CRF: the difference between the NDR group and the NDM group was not statistically significant (P>0.05). The results of multiple linear regression analysis showed that CCT and IOPcc in DR patients were independent influencing factors of CH [CCT: β=0.01, 95% confidence interval (CI) 0.01-0.03, P=0.013; IOPcc: β=－0.15, 95%CI －0.25-－0.05, P=0.005]; Age, CCT, IOPcc were independent influencing factors of CRF [Age: β=－0.06, 95%CI －0.09-－0.03, P＜0.001; CCT: β=0.01, 95%CI 0.00-0.02, P=0.049; IOPcc: β=0.16, 95%CI 0.07-0.25, P=0.001]. The comparison of CCT, CH, CRF, adjusted CH, and adjusted CRF of the eyes in the NDR group, NPDR group, and PDR group were statistically significant (F=3.76, 5.36, 12.61, 6.59, 10.41; P<0.05). Pairwise comparison between groups, CH, CRF, adjusted CH, adjusted CRF: the difference between the NPDR group, the PDR group and the NDR group was statistically significant (P<0.05), and the difference between the PDR group and the NPDR group was not statistically significant (P>0.05); CCT: The difference between NPDR group and NDR group, PDR group and NPDR group was not statistically significant (P>0.05), and the difference between PDR group and NDR group was statistically significant (P<0.05). ConclusionThe CH and CRF of eyes with T2DM and DR are elevated; CCT and IOPcc are independent influencing factors of CH, and age, CCT and IOPcc are independent influencing factors of CRF.
Age-related macular degeneration is one of the major causes of blindness in the elderly. As an important pathway of cell metabolism, autophagy maintains intracellular homeostasis through the degradation and recycle of damaged organelles and macromolecules. Understanding its mechanism may promote discoveries to delay aging process, reduce the incidence of age-related diseases. In mammals, silent information regulator protein 6 (SIRT6) plays its deacetylase and ribonucleotransferase activity in multiple signaling pathways, including inhibition of cellular senescence, tumorigenesis, metabolic diseases, regulating cellular lifespan. It has a significant impact on the structure and function of tissues and organs. SIRT6 regulates intracellular autophagy mainly through the insulin-like growth factor-protein kinase B-mammalian target of rapamycin, reducing the accumulation of toxic metabolites and cellular senescence. The function of SIRT6 in age-related macular degeneration need to be combined with the genetic background, pathogenesis, clinical manifestations and other aspects of the disease, and it is expected to be further studied in subsequent studies.
Objective To investigate the prevalence and related factors of diabetic retinopathy (DR) among residents with type 2 diabetes mellitus (T2DM) in Culai Town of Tai'an City in Shandong Province. Methods According to the DM management file database for community, 785 patients with T2DM were randomly selected by cluster sampling method. The questionnaires, routine general examinations, visual and fundus-free fluoroscopy were performed on all the patients. DR diagnosis and classification was according to the guidelines for clinical diagnosis and treatment of DR in China (2014). Both monocular and binocular DR were selected as DR patients, and the worse eye for binocular DR were treated as the DR classification of the patient. The patients were grouped by presence or absence of DR. GraphPad Prism 6, SigmaPlot 12.5, SPSS 20.0 and Excel were used to achieve data analysis. Also, SPSS 20.0 was used for multi-factor logistic regression analysis. Results A total of 699 patients (89.04%) were actually recorded. There were 122 eyes of 63 patients (9.01%) with DR (DR group), 1272 eyes of 636 patients (90.99%) without DR (NDR group). Among the 122 eyes of DR, there were 19 (15.57%), 17 (13.93%), 70 (57.38%), 10 (8.20%), 6 (4.92%) eyes in stage Ⅰ, Ⅱ, Ⅲ, Ⅳ, Ⅴ, respectively. The differences of mean age (t=15 290, P=0.002), DM duration (t=9075, P＜0.000) and diastolic blood pressure (t=15 810, P=0.006) between the two groups were statistically significant. There were 23 (36.51%) and 394 (61.95%) patients with hypertension history in the DR group and the NDR group, with the significant difference ( χ2=15.42, OR=0.35, 95%CI 0.21-0.60). There were 57 (90.48%) and 500 (78.62%) patients with fasting blood glucose larger than 6.11 mmol/L in the DR group and the NDR group, with the significant difference (OR=2.51, 95%CI 1.06-5.95, P=0.031). Logistic regression analysis showed that the age, fasting blood glucose and DM duration were influencing factors for DR (OR=1.039, 0.864, 0.898; P=0.021, ＜0.000, ＜0.000). Conclusion The prevalence of DR in patients with T2DM in Culai Town of Tai'an City is 9.01%. Age, DM duration, fasting blood glucose are associated to DR. Those with a history of hypertension may have a lower risk of DR than those without a history of hypertension.
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)
ObjectiveTo observe the influence of human umbilical cord mesenchymal stem cells (hUCMSC) transplantation into vitreous cavity of diabetic rats on the retinal morphology, and the expression of glial fibrillary acidic protein (GFAP) and rhodopsin (RHO). Methods78 male Sprague-Dawley rats were used. 70 rats were injected with streptozotocin by tail vein injection at a dose of 40 mg/kg to establish the diabetes mellitus model, and another 8 rats were injected with 0.1 mol/L pH 4.0 citric acid buffer at the same dose as the normal control group. After 6 weeks of modeling, 10 rats were taken as the control group of diabetic model. hUCMSC suspension was injected into the right eye vitreous cavity of the remaining 60 rats, and the same volume of Dulbecco's modified Eagle/F12 medium was injected into the left vitreous cavity as control eyes. 1, 2 and 4 weeks after transplantation, follow-up experiments were performed. The experimental eyes were labeled as U1, U2, and U4 groups, while the control eyes were recorded as D1, D2, D4, and each group consisted of 20 eyes. After paraffin section and hematoxylin-eosin staining, the structure of the retina was observed by optical microscopy and the thickness of the outer nuclear layer and the inner nuclear layer (INL) were measured. The distribution and migration of hUCMSC in rat retina were observed by frozen section-tissue immunofluorescence assay. The mRNA and protein expression of GFAP and RHO in the retina were detected by real-time quantitative polymerase chain reaction (PCR) and Western blot assays. ResultsThe results of optical microscope observation showed the normal structure of retina in normal control group. The retinal nerve fiber layer (NFL) was thinned and the number of retinal ganglion cells (RGC) in the control group of diabetic rats was decreased. The decreased number and disorder arrangement of RGC were observed as well in U1, D1 rats. The RGC number of U2, U4, D2, D4 rats was gradually decreased. Compared with D4 group, the thickness of INL in U4 group was significantly increased (P < 0.05). Tissue immunofluorescence assay showed that hUCMSC were distributed along the inner limiting membrane in the retina of the U1 group, while the number of hUCMSC in the U2 group was gradually decreased, mainly in the NFL and ganglion cell layers. Real-time PCR and Western blot data indicated that the relative expression of GFAP mRNA and protein in the diabetic retina was significantly increased, and the relative expression of RHO mRNA and protein decreased gradually in the diabetic model group and the D1, D2, D4 groups. Compared with D2 and D4 groups, the mRNA and protein expression of GFAP in U2 and U4 groups were decreased, and the relative expression of RHO mRNA and protein were all increased (P < 0.01). ConclusionhUCMSC could migrate and integrate into the retina, after the transplantation into the vitreous cavity of diabetic rats, which reduced the expression of GFAP, but enhanced the expression of RHO.
Diabetic macular edema (DME) is the main cause of visual impairment in diabetic retinopathy patients. It mainly includes focal DME and diffuse DME, while DME of clinical significance needs timely intervention treatment. Optical coherence tomography is currently recognized as the most sensitive method to accurately diagnose DME. Currently, the common treatments of DME include intravitreal injection of anti-vascular endothelial growth factor (VEGF) or glucocorticoid and laser photocoagulation. Among them, anti-VEGF injection is becoming the first-line therapeutic, and corresponding individual treatment or combined treatment strategy should be selected according to the characteristics of DME and the specific conditions of patients. During the diagnosis and treatment of DME, attention should be paid to the systemic treatment of diabetes and the effect of diabetes-related neuroretinopathy on the therapeutic effect of DME. With the appearance of heterogeneity in the efficacy of anti-VEGF drugs, it remains to be further studied how to choose alternative therapeutics and when to replace them.
The fovea avascular area (FAZ) is an area of the retina surrounded by a continuous capillary plexus that does not have any capillary structure of its own. FAZ is an important region for the formation of fine vision function. The changes of its morphology and surrounding capillary density reflect the degree of macular ischemia, and are closely related to retinal vascular diseases such as diabetic retinopathy, retinal vein occlusion, Coats disease, idiopathic macular telangiectasia, and retinopathy of prematurity. Early observation of FAZ region changes in patients with retinal vascular disease by optical coherence tomography angiography (OCTA) can evaluate the severity and prognosis of the disease. However, the measurement error of FAZ-related data is still a problem that cannot be ignored. At present, OCTA devices of various manufacturers have different methods and algorithms for measuring and analyzing FAZ, which makes it impossible to compare the measured data between different devices. It is believed that with the continuous progress of OCTA related technology, more accurate data of FAZ regional changes can be obtained, which will bring more help to clinical work.