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 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)
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.
Objective To investigate the early influences of laser photocoagulation on macular retinal thickness in diabetic retinopathy(DR). Methods Optic coherence tomography examination was performed in 30 eyes with DR(phase Ⅲ~Ⅳ) before, and on the 3rd day and the 7th day after photocoagulation respectively. The thickness of neuroretina and pigment epithelium were measured in the areas of fovea macula and 750 μm from fovea macula. Results Three days after photocoagulation, significant thickening of neuroretina was observed in the fovea macula, which is positively related with age, fasting blood sugar and duration of DR. There was no significant changes in the thickness of pigment epithelium in macula and in the thickness of neuroretina 750 μm from fovea macula. Conclusion Significant thickening of neuroretina in fovea macula in DR early after photocoagulation reveals progressed macular edema induced by photocoagulation which is positively related with age, fasting blood sugar and duration of DR. (Chin J Ocul Fundus Dis, 2002, 18: 31-33)
The mechanisms behind diabetic retinopathy (DR) can be ascribed primarily to retinal microvascular abnormalities, excessive inflammatory response and neurodegeneration. Circular RNA (circRNA) is a type of endogenous non-coding RNA with a special circular structure, which is mainly composed of precursor RNA after shearing and processing. It is widely present in the retina and participates in the occurrence and development of various fundus diseases. CircRNAs express in an abnormal way in retina, serving as “the sponge” for miRNA so as to play roles in dysfunction of retinal vascular, inflammatory response and neurodegeneration in the development of DR. Further studies for circRNAs in DR will illustrate pathophysiology of DR more deeply, shedding light on circRNAs becoming novel biomarkers and molecular targets for diagnosis and treatment, thus achieving the goal of early diagnosis and precise therapy of DR.
Deep learning-based automatic classification of diabetic retinopathy (DR) helps to enhance the accuracy and efficiency of auxiliary diagnosis. This paper presents an improved residual network model for classifying DR into five different severity levels. First, the convolution in the first layer of the residual network was replaced with three smaller convolutions to reduce the computational load of the network. Second, to address the issue of inaccurate classification due to minimal differences between different severity levels, a mixed attention mechanism was introduced to make the model focus more on the crucial features of the lesions. Finally, to better extract the morphological features of the lesions in DR images, cross-layer fusion convolutions were used instead of the conventional residual structure. To validate the effectiveness of the improved model, it was applied to the Kaggle Blindness Detection competition dataset APTOS2019. The experimental results demonstrated that the proposed model achieved a classification accuracy of 97.75% and a Kappa value of 0.971 7 for the five DR severity levels. Compared to some existing models, this approach shows significant advantages in classification accuracy and performance.