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Diabetic retinopathy (DR) is One of the most wellknown microvascular complications of diabetes mellitus (DM) and is a frequent side effect of untreated diabetes that can lead to blindness and visual impairment. This study was conducted to assess the prevalence of diabetic retinopathy and associated factors among type 2 diabetic patients. A cross sectional study was done at Ajdabiya diabetic center from November 2023 to January 2024. Subjects and Methods: 52 patients (104 eyes) with T2DM were included in this study, their fasting blood sugar and glycosylated hemoglobin level, lipid profile measured.in addition to fundus examination (done by noncontact +90-diopter lens), fundus photographs taken by Non-Mydriatic Fundus Camera TFC-1000. Around 61 eyes (58.7%) had diabetic retinopathy, 27 eyes (26%) had back ground DR, 6 eyes (5.8 %) had pre-proliferative DR, 4 eyes (3.8%) had proliferative DR, 2 eyes (1.9%) had advanced diabetic eye disease, 22 eyes (21.2%) had CSME. Their ages ranges between 3674 years with mean (58.90) years, (26.9%) were males, (73.1%) were females. There was a significant association between the development of DR and duration of DM (p=0.003), The FBS levels were also determined to be a significant risk factor for DR (p = 0.031), also LDL with (p=0.039). No other factors were found to have a significant association with DR. In this study more than half of diabetic patients had diabetic retinopathy. There was a significant association between the development of DR and duration of DM, FBS, LDL levels, there was no significant relation between diabetic retinopathy and hypertension, HgA1c Serum cholesterol or triglyceride levels or previous cataract surgery.
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Humans , Male , Female , Diabetic RetinopathyABSTRACT
Objective To investigate the expression of long non-coding RNA(lncRNA)LINC02695 in human retinal microvascular endothelial cells(HRMECs)in high glucose(HG)environment and its effect on the proliferation,migration and neovascularization of HRMECs.Methods HRMECs was divided into four groups:the normal glucose(NG)group(5.5 mmol/L),the HG group(30.0 mmol/L),the HG+LINC02695 silenced group(HG+si-LINC02695),and the HG+silenced control group(HG+si-NC).Real-time quantita-tive fluorescent PCR(qPCR)was used to detect the expression of LINC02695 and vascular endothelial growth factor(VEGF)mRNA in HRMECs of each group.The cell proliferation of each group was measured by Cell Counting Kit-8(CCK-8)method.The migration ability of cells in each group was detected by Transwell as-say.The tube forming ability of cells in each group was detected by tube forming experiment.Results The qPCR results showed that compared with the NG group,LINC02695 and VEGF were highly expressed in the HG group(P＜0.05).Compared with the HG group,VEGF mRNA expression level in the HG+si-LINC02695 group was significantly decreased(P＜0.05).The results of CCK-8 experiment showed that the proliferation ability of the HG group was significantly enhanced compared with the NG group(P＜0.05).Compared with the HG group,the cell proliferation ability of the HG+si-LINC02695 group was significantly decreased(P＜0.05).The results of Transwell experiment showed that the cell migration ability of the HG group was significantly increased compared with the NG group(P＜0.05).Compared with the HG group,the cell migration ability of the HG+si-LINC02695 group was significantly decreased(P＜0.05).The results of tube formation experiment showed that compared with the NG group,the tube formation ability of the HG group was significantly increased(P＜0.05).Compared with the HG group,canalization ability of cells in the HG+si-LINC02695 group was significantly decreased(P＜0.05).Conclusion LINC02695 may be involved in promoting the proliferation,migration and angiogenesis of HRMECs induced by HG.
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Objective To investigate the relationship between serum microRNA(miR)-137 and miR-21 ex-pression and hypertensive retinopathy(HR).Methods A total of 123 hypertensive patients admitted to the hospital from March 2020 to August 2022 were selected as the hypertensive group and divided into HR and non-HR groups according to whether they were concomitant with HR,and another 58 healthy people who un-derwent the physical examination during the same period were selected as the control group.Clinical data of HR patients were collected and serum miR-137 and miR-21 expression was detected by real-time fluorescent quantitative PCR.The influencing factors of concurrent HR in hypertensive patients were analyzed,and receiv-er operating characteristic(ROC)curve was used for analzing predictive value of serum miR-137 and miR-21 expression in hypertensive patients with concurrent HR.Results Serum miR-137 and miR-21 relative expres-sion levels were higher in the hypertensive group than those in the control group(P<0.05).The incidence rate of HR in 123 hypertensive patients was 25.20%(31/123).Multivariate Logistic regression analysis showed that prolonged duration of hypertension and elevated systolic pressure,diastolic pressure,miR-137 rel-ative expression level,and miR-21 relative expression level were independent risk factors for HR in hyperten-sive patients(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of serum miR-137 combined with miR-21 in predicting HR in hypertensive patients was 0.840,which was greater than 0.735 and 0.732 of the single detection of miR-137 and miR-21(P<0.05).Conclusion High expression of serum miR-137 and miR-21 is closely associated with hypertension complicating HR and may be an auxiliary predictor of HR.
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Objective To analyze the correlation between serum miR-939 and miR-15b expression and mi-crovascular injury in patients with diabetic retinopathy(DR).Methods A total of 176 patients with type 2 di-abetes diagnosed and treated in the Baoding Second Hospital from January 2021 to October 2022 were selected as the study objects.The subjects were divided into 74 patients without DR(NDR group),62 patients with non-proliferative DR(NPDR group)and 40 patients with proliferative DR(PDR group)according to whether or not DR occurred and the degree of lesions.Real-time fluorescent quantitative PCR was used to detect the relative expression levels of miR-939 and miR-15b in serum of all groups,the level of vascular endothelial growth factor(VEGF)was detected by enzyme-linked immunosorbent assay,and the count percentage of en-dothelial cells(ECs),endothelial progenitor cells(EPCs)and circulating progenitor cells(CPCs)was detected by flow cytometry.Serum levels of miR-939,miR-15b,VEGF and ECs,EPCs and CPCs were compared in 3 groups.Pearson correlation was used to analyze the correlation between serum miR-939 and miR-15b and VEGF,ECs,EPCs and CPCs.Multivariate Logistic regression was used to analyze the factors affecting the oc-currence of DR in patients with type 2 diabetes.Results The relative expression levels of miR-939 and miR-15b in PDR group and NPDR group were lower than those in NDR group,while the serum VEGF levels were higher than those in NDR group,with statistical significance(P＜0.05).ECs in PDR group and NPDR group were higher than those in NDR group,while EPCs and CPCs were lower than those in NDR group,the differ-ence was statistically significant(P＜0.05).Serum miR-939 was negatively correlated with VEGF and ECs(r=-0.407,-0.613,P＜0.05),and positively correlated with EPCs and CPCs(r=0.481,0.486,P＜0.05).Serum miR-15b was negatively correlated with VEGF and ECs(r=-0.539,-0.625,P＜0.05),and positively correlated with EPCs and CPCs(r=0.451,0.483,P＜0.05).Multivariate Logistic regression anal-ysis showed that the duration of type 2 diabetes,hemoglobin A1c,2-hour postprandial blood glucose,VEGF,miR-939 and miR-15b were the influencing factors for the occurrence of DR in type 2 diabetes patients(P＜0.05).Conclusion The expression of miR-939 and miR-15b in serum of DR patients is closely related to VEGF,ECs,EPCs and CPCs,and the expression of miR-939 and miR-15b in serum of DR patients can provide a certain reference for early judgment and evaluation of the degree of microvascular injury.
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Objective To compare the clinical efficacy of anti-vascular endothelial growth factor(VEGF)combined with pars plana vitrectomy(PPV)treatment for patients with proliferative diabetic retinopathy(PDR)of different traditional Chinese medicine(TCM)syndrome types in the real world.Methods A prospective real-world study was performed in the 36 patients(involving 42 eyes)with PDR treated by anti-VEGF combined with PPV in the Department of Ophthalmology of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from March 2019 to December 2019.According to the TCM syndrome manifestations,the patients were differentiated as qi-yin deficiency complicated with blood stasis obstructing collaterals type(15 cases,involving 18 eyes;shorten as qi-yin deficiency type),liver-kidney deficiency and ocular collaterals failing in the nourishment type(14 cases,involving 17 eyes;shorten as liver-kidney deficiency type),and yin-yang deficiency complicated with blood stasis and phlegm coagulation type(7 cases,involving 7 eyes;shorten as yin-yang deficiency type).The patients were treated with anti-VEGF therapy first and then received PPV after 5-7 days.Aqueous humor was sampled during anti-VEGF therapy and PPV.After treatment,the efficacy of PDR patients with different TCM syndromes was compared.Moreover,the patients were observed in the best corrected visual acuity(BCVA)of the affected eyes before surgery and 3 months after surgery,levels of cytokines in the aqueous humor before and after anti-VEGF treatment,macular central retinal thickness(CRT),area of the foveal avascular zone(FAZ),the blood density of macular center,inner ring,outer ring and intact macula 3 months after surgery,and the postoperative complications.Results(1)The difference of the therapeutic efficacy of PDR patients with various TCM syndrome types was statistically significant(P＜0.05).Among 3 syndrome types,the best efficacy was found in the qi-yin deficiency type,followed by liver-kidney deficiency type,and then yin-yang deficiency type,with the total efficacy rate being 88.89%(16/18),52.94%(9/17),and 42.86%(3/7),respectively.(2)Three months after surgery,the logarithmic value of minimum angle of resolution(LogMAR)for BCVA of patients with qi-yin deficiency type was significantly superior to that of patients with yin-yang deficiency type,with the difference being statistically significant(P＜0.05).After the anti-VEGF treatment,the levels of cytokines in the aqueous humor of the patients varied in the 3 syndrome types:vascular endothelial growth factor A(VEGF-A)level in the patients with the 3 syndrome types was significantly lower,placental growth factor(PLGF)and angiopoietin-like protein 4(ANGPTL4)levels in the patients with qi-yin deficiency type were higher,and interleukin 8(IL-8)level in the patients with liver-kidney deficiency type was higher than those before treatment,and the differences were statistically significant(P＜0.05 or P＜0.01).The blood density of macular outer ring and intact macula in the patients with qi-yin deficiency type and liver-kidney deficiency type was larger than that in the patients with yin-yang deficiency type,and the differences were statistically significant(P＜0.05).However,the differences of CRT,FAZ area,and blood density of macular center and inner ring among the 3 syndrome types were not statistically significant(P＞0.05).(3)The incidence of postoperative complications in the patients with yin-yang deficiency type was relatively high,but the difference among the 3 syndrome types was not statistically significant(P＞0.05).Conclusion In the real world,the best efficacy of anti-VEGF combined with PPV treatment in PDR patients with different TCM syndrome types can be achieved in the patients differentiated as qi-yin deficiency type,followed by liver-kidney deficiency type,and then yin-yang deficiency type.After anti-VEGF treatment,the levels of cytokines in the aqueous humor of the patients vary in the 3 syndrome types.Three months after the operation,the patients with qi-yin deficiency type and liver-kidney deficiency type have larger blood density of macular outer ring and intact macula,and exert good prognosis.
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Objective:To investigate the relationship between health promoting behavior and frailty in elderly patients with proliferative diabetic retinopathy(PDR),and the mediating effects of self-efficacy and loneliness.Methods:In an eye hospital of Anhui Province,214 elderly patients with PDR were selected from May 2021 to Nov 2022 by convenient sampling method.The Frailty Scale,Chinese Version of Health-Promoting Lifestyle Profile-Ⅱ,Self-Efficacy Scale and Simplified Loneliness Scale were used in this survey.Bootstrap method of Process software was used to analyze the mediating effect of self-efficacy on the relationship between health promoting behaviors and frailty in elderly PDR patients and the moderating effect of loneliness on the relationship between self-efficacy and frailty.Results:A total of 220 questionnaires were distributed and 214 valid questionnaires were returned,with valid response rate of 97.27% .Moderated mediation effect analysis suggested that health-promoting behaviors negatively predicted frailty(β=-0.508,P＜0.01).Health promoting behaviors and self-efficacy had significant predictive effects on frailty(β=-0.191 and-0.433,P＜0.01),and health promoting behaviors also had a significant predictive effect on self-efficacy(β=0.063,P＜0.01).Self-efficacy played a partially mediating role between health promoting behaviors and frailty,and the mediating effect accounted for 14.76% of the total effect.The product term of loneliness and self-efficacy significantly predicted frailty(β=0.255,P＜0.01),the mediating effect of self-efficacy on frailty was moderated by loneliness.Conclusions:The health-promoting behaviors of elderly patients with PDR affect frailty through self-efficacy,and loneliness moderates the relationship between self-efficacy and frailty.The moderated mediation model is established.
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Objective To study the changes in serum autophagy markers in children with retinopathy of prematurity(ROP)and its clinical value.Methods Premature infants who were screened for ROP in our hospital from January 2020 to December 2022 were selected as the study subjects.Those screened out with ROP at 4-6 weeks of birth were assigned to the ROP group and those without ROP to the control group.The levels of serum autophagy markers LC3-Ⅱ,Beclin-1 and P62 were detected at the 3rd day,1st,2nd and 3rd weeks of birth.The two groups were compared in terms of serum autophagy markers.The diagnostic efficacy of serum autophagy markers on ROP was analyzed.Results There was no significant difference in serum LC3-Ⅱ,Beclin-1 and P62 levels between the ROP group and control group at the 3rd day of birth(P>0.05).At the first,second and third weeks of birth,how-ever,the ROP group showed significantly lower levels of serum LC3-Ⅱ and Beclin-1 but higher level of P62 com-pared to the control group(both P<0.05).The levels of serum LC3-Ⅱ,Beclin-1 and P62 at the first,second and third weeks of birth had diagnostic value for ROP.The children in the ROP group who did not receive mechanical ventilation and oxygen inhalation,and did not develop with sepsis and bronchopulmonary dysplasia showed lower serum LC3-Ⅱ and Beclin-1 levels and higher P62 levels at the first,second and third weeks of birth compared to those without the above-mentioned treatment as well as those complications(all P<0.05).In the ROP group,those with severe ROP showed lower serum LC3-Ⅱ and Beclin-1 levels and higher P62 levels at the 3rd day,and 1st,2nd and 3rd week of birth(all P<0.05).Conclusion The levels of serum autophagy markers in children with ROP show significant changes since the first week of birth,so they have diagnostic efficacy for the diseases.
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Objective:We applied a hypoxia-induced model of human fetal retinal microvascular endothelial cell (RMEC) to study the effect of carbonic anhydrase 9 (CA9) on cell proliferation.Methods:The eyeballs of spontaneously aborted fetuses in Guangdong Women and Children's Hospital were obtained, and the retinas were isolated. RMEC was obtained by trypsin and collagenase two-step enzyme digestion, and endothelial cells were identified by CD34. The fetal RMEC and the purchased adult RMEC were cultured in normoxic and hypoxic incubators (1%O 2+5%CO 2+94%N 2), and the expression of CA9 was detected by qPCR and Western blot. After knocking down the CA9 by small interference RNA technique, the cell proliferation was detected by CCK-8 method, and the cell viability was detected by CCK-8 after adding CA9 inhibitor U-104. Results:The primary RMEC was extracted successfully. Immunofluorescence staining showed the percentage of CD34 positive cells in the third-generation cells was nearly 100%. The expression of CA9 mRNA in immature fetus and adult RMEC under hypoxia culture was higher than that under normoxic culture (fetal 1% O 2 group vs. fetal 21% O 2 group: 67.80±10.31 vs. 1.00±0.04, P<0.001; adult 1% O 2 group vs. adult 21% O 2 group: 1.72±0.22 vs. 1.00±0.02, P=0.014). Western blot analysis showed significantly increased expression of CA9 in the fetal RMEC exposed to hypoxia, which aligned with the expression of CA9 mRNA. When fetal RMEC was transfected with siCA9 20 nM, the knockdown rate of CA9 was 95% ( P<0.001). CCK-8 assay showed significantly lower proliferation of fetal RMEC cells in siCA9 group compared to siNC group (0.57±0.05 vs. 0.90±0.03, P<0.001), which was reflected by the OD value. With the addition of 100 μM CA9 inhibitor U-104, the viability of fetal RMEC in the treated groupwas significantly lower than that in the untreated group (99.16%±3.82% vs. 119.10% ±1.72%, P=0.002). Conclusions:The expression of CA9 differed between adult and preterm fetus in our hypoxia-induced RMEC model. Inhibiting CA9 can inhibit the proliferation of retinal microvascular endothelial cells of preterm fetus.
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Diabetic retinopathy(DR)is considered to be a chronic medium-and low-grade inflammatory disease(mi-croinflammation).Inflammation runs through the entire process of DR,manifesting as an increase in ocular and systemic inflammation biomarkers.In the eyes of DR patients,there is an increase in pro-inflammatory mediators,such as interleu-kin(IL)-1 β,IL-6 and tumor necrosis factor-α,as well as activated and increased number of inflammatory cells,such as ac-tivated microglia,Müller cells in the retina,and infiltration of mononuclear macrophage.In addition,immunocytes are also involved in the pathogenesis of DR,such as the involvement of circulating T cells in leukostasis.These indicate that chronic inflammation is an inducing factor of DR,with multiple inflammation-related factors participating and influencing each other,leading to the destruction of the blood-retinal barrier and neuronal injury and exacerbating the development of DR.There-fore,personalized anti-inflammatory therapy is of great significance in the treatment of DR.
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Diabetic retinopathy(DR)is a common complication of diabetes.Sodium-glucose cotransporter 2(SGLT-2)inhibitors are widely used in diabetic patients as hypoglycemic drugs and also play a role in the prevention and treatment of DR.At present,there has been no systematic study on the clinical treatment of DR by SGLT-2 inhibitors.This paper re-views the research progress of SGLT-2 inhibitors in the treatment of DR,in order to provide more ideas for the clinical treatment of DR.
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Objective To investigate the influencing mechanism of micro ribonucleic acid(miR)-375 targeting phos-phatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway on high glucose-induced proliferation and angiogenesis in human retinal endothelial cells(hRECs).Methods The hRECs were cultured in vitro,and transfection and dual lucifer-ase assay were performed on them.These hRECs were divided into the control group,high glucose group,high glucose+miR-375 group,and high glucose+miR-375+LM22B-10 group.The Cell Counting Kit-8 was used to detect the cell prolifera-tion ability,the angiogenesis assay was used to detect the vascular formation ability,real-time quantitative PCR was used to detect the miR-375 and PI3K mRNA expressions in hRECs,and Western blot was used to detect the PI3K and p-AKT/AKT protein expressions in hRECs.Results At 48 h and 72 h after the cultivation,compared with the control group,the pro-liferation viability,PI3K and p-AKT/AKT protein expressions,vascular formation ability,and PI3K mRNA expression in hRECs significantly increased,and the miR-375 expression in hRECs significantly decreased in the high glucose group,high glucose+miR-375 group and high glucose+miR-375+LM22B-10 group(all P＜0.05).Compared with the high glucose group,the proliferation viability,PI3K mRNA and protein expressions,p-AKT/AKT protein expression and vascular forma-tion ability in hRECs were significantly reduced,and miR-375 expression significantly increased in the high glucose+miR-375 group(all P＜0.05).Compared with the high glucose+miR-375 group,the proliferation viability,vascular formation a-bility and p-AKT/AKT protein expression in hRECs significantly increased in the high glucose+miR-375+LM22B-10 group(all P＜0.05);there was no significant difference in the miR-375 and PI3K mRNA(all P＞0.05).After transfected with miR-375 mimic and wt-PI3K-pGL4,the relative luciferase activity in hRECs significantly decreased compared with transfec-tion with miR-375 NC and mut-PI3K-pGL4(all P＜0.05).Conclusion The targeted inhibition of the PI3K/AKT pathway by miR-375 can suppress the high glucose-induced proliferation and angiogenesis of hRECs,alleviating DR.
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Objective To investigate the effect of evodiamine(EVO)on retinal injury in diabetic rats by regulating the cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)signaling pathway.Methods Totally 96 Sprague-Dawley rats(192 eyes)were divided into the negative control(NC)group,Model group,low-dose EVO(EVO-L)group,medium-dose EVO(EVO-M)group,high-dose EVO(EVO-H)group,calcium dobesilate(CD)group,SQ22536 group and EVO-H+SQ22536 group,with 12 rats in each group.Rats in the NC group were intraperitoneally injected with physiological saline instead of streptozotocin,and diabetic retinopathy models were established in all other groups.After successful mod-eling,the drug was administered once a day for 4 weeks.The blood glucose level of rats in each group was measured by blood glucose meter;HE staining was applied to detect the pathological changes of the retina of rats;TUNEL staining was adopted to detect the apoptosis of ganglion cells in the retina of rats;the levels of superoxide dismutase(SOD),malondial-dehyde(MDA),tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and cAMP in the retina of rats were detected;West-em blot was used to detect the protein expressions of Bcl-2 associated X protein(Bax),P53 and phosphorylated protein ki-nase A(p-PKA)in the retina of rats.Results Compared with the NC group,the pathological injury of the retina in the Model group was more serious;the blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions increased,and the SOD,cAMP and p-PKA/PKA protein expression decreased,with statistically significant differences(all P＜0.05).Compared with the Model group,the pathological injury of the retina was relieved,the blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions decreased,and the SOD,cAMP and p-PKA/PKA protein expression increased in the EVO-L group,EVO-M group,EVO-H group and CD group,with statistically significant differences(all P＜0.05).Compared with the Model group,the retinal tissue of the SQ22536 group was severely damaged,the blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions increased,and the SOD,cAMP,p-PKA/PKA protein expression decreased,with statistically significant differences(all P＜0.05).Compared with the EVO-H group,the EVO-H+SQ22536 group showed more serious pathological injury of retinal tissue,increased blood glucose,apoptosis rate of retinal ganglion cells,MDA,TNF-α,IL-6,Bax and P53 protein expressions,and decreased SOD,cAMP and p-PKA/PKA protein expression,and the differences were statistically significant(all P＜0.05).Conclusion EVO may alleviate retinal injury in diabetic rats by activating the cAMP/PKA signaling pathway.
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Objective To evaluate the relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM)based on imaging and clinical testing data.Methods Totally 600 T2DM patients who visited the First People's Hospital of Ziyang from March 2021 to December 2022 were included.The fundus photography and fundus fluorescein angiography were performed on all these patients and their age,gender,T2DM duration,cardiovascular diseases,cerebrovascular disease,hypertension,smoking history,drinking history,body mass in-dex,systolic blood pressure,diastolic blood pressure and other clinical data were collected.The levels of fasting blood glu-cose(FPG),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipo-protein cholesterol(LDL-C),glycosylated hemoglobin(HbA1c),24 h urinary albumin(UAlb),urinary albumin to creati-nine ratio(ACR),serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.Logistic regression was used to analyze the risk factors associated with DR.DR staging was performed according to fundus images,and the convolutional neural network(CNN)algorithm was used as an image analysis method to explore the correlation between DR and DN based on emission computed tomography(ECT)and clinical testing data.Results The average lesion area rates of DR and DN detected by the CNN in the non-DR,mild-non-proliferative DR(NPDR),moderate-NPDR,severe-NPDR and pro-liferative DR(PDR)groups were higher than those obtained by the traditional algorithm(TCM).As DR worsened,the Scr,BUN,24 h UAlb and ACR gradually increased.Besides,the incidence of DN in the non-DR,mild-NPDR,moderate-NPDR,severe-NPDR and PDR groups was 1.67％,8.83％,16.16％,22.16％and 30.83％,respectively.Logistic regression analysis showed that the duration of T2DM,smoking history,HbA1c,TC,TG,HDL-C,LDL-C,24 h UAlb,Scr,BUN,ACR and glomerular filtration rate(GFR)were independent risk factors for DR.Renal dynamic ECT analysis demonstrated that with the aggravation of DR,renal blood flow perfusion gradually decreased,resulting in diminished renal filtration.Conclusion The application of CCN in the early stage DR and DN image analysis of T2DM patients will improve the diag-nosis accuracy of DR and DN lesion area.The DN is worsening as the aggravation of DR.
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Objective To investigate the impact of the interaction of fasting blood glucose(FBG)and serum uric acid(SUA)on diabetic retinopathy(DR).Methods A total of 306 diabetes mellitus(DM)patients diagnosed and re-ceived comprehensive ophthalmic examination in the First Affiliated Hospital of Gannan Medical University from January 2019 to January 2021 were selected.According to the presence or absence of DR,these patients were divided into the DR group(178 patients)and the non-DR(NDR)group(128 patients).The general clinical data of patients in the two groups were compared.The least absolute shrinkage and selection operator(LASSO)regression method and multivariate Logistic regression analysis were used to screen the independent influencing factors of DR in DM patients,and the odds ratio of risk factors was calculated.The sensitivity analysis of the results was performed using the E-value method.The interaction of FBG and SUA on DR in DM patients was analyzed by an additive interaction model.The Nomogram model to predict DR in DM patients was constructed and verified internally.The receiver operating characteristic curve(ROC)was used to evalu-ate the effects of FBG,SUA and both FBG and SUA on DR in DM patients.Results Compared with the NDR group,the course of DM in the DR group was significantly longer,the proportion of patients with history of oral medication was signif-icantly lower,the proportion of patients with history of insulin therapy was significantly higher,and the levels of total cho-lesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,blood urea nitrogen,serum creatinine,SUA and FBG were significantly higher(all P＜0.05).The history of insulin therapy,course of DM≥9.66 years,TG≥2.07 mmol·L-1,SUA ≥ 297.73 μmol·L-1 and FBG ≥8.92 mmol·L-1 were the risk factors for DR in DM pa-tients,while the history of oral medication was the protective factor for DR in DM patients.The Nomogram model based on the above independent risk factors was accurate in predicting the occurrence of DR in DM patients.SUA and FBG had inter-active effects on DR in DM patients.The value of SUA-FBG interaction in the diagnosis of DR was greater than that of both alone.Conclusion SUA≥ 297.73 μmol·L-1 and FBG ≥8.92 mmol·L-1 are the risk factors for DR in DM patients.The value of interaction of FBG and SUA in the diagnosis of DM accompanied by DR is greater than that of both alone.
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Objective To explore the mechanism of micro ribonucleic acid(miR)-3197 in diabetic retinopathy(DR)on the basis of the nuclear factor κB(NF-κB)signaling pathway.Methods A total of 47 DR patients admitted to Heng-shui People's Hospital from January 2021 to December 2021 were selected as the DR group,and 47 healthy individuals in the same period were collected as the control group.Their information in gender,age,fasting blood glucose(FBG),fast-ing insulin(FINS),triglycerides(TG),total cholesterol(TC)and miR-3197 were compared.The correlation between miR-3197 in DR patients and laboratory data was analyzed,and the receiver operating characteristic(ROC)curve of miR-3197 for DR diagnosis was drawn.The human retinal microvascular endothelial cells(hRMECs)were cultured in vitro and treated with 5.5 mmol·L-1 glucose[low glucose(NG)group]and 30 mmol·L-1 glucose[high glucose(HG)group],respectively.After transfecting with anti-miR-NC and anti-miR-3197,the cells were treated with 30 mmol·L-1 glucose(HG+anti-miR-NC group and HG+anti-miR-3197 group).Real-time fluorescence quantitative PCR was used to detect the relative expression level of miR-3197,flow cytometry was used to detect the apoptosis rate of hRMECs,enzyme-linked im-munosorbent assay was used for detecting tumor necrosis factor-a(TNF-a)and interleukin-6(IL-6),and Western blot was adopted to detect the expressions of aspartic protease 3 containing cysteine(cleaved caspase-3)protein,Bax protein and NF-κB signaling pathway-related proteins[phospho-NF-KB p65(p-p65),p65,phospho-NF-KB inhibited protein(p-IκBα),and NF-κB inhibited protein(IκBα)].Results The levels of FBG,FINS,TC and TG in the DR group were higher than those in the control group,and the differences were statistically significant(all P＜0.001).The relative expression level of miR-3197 in the peripheral blood of patients in the DR group(2.76±0.67)was higher than that of the control group(1.03±0.34),and the difference was statistically significant(P＜0.05).The miR-3197 level of patients in the DR group was positively correlated with FBG,FINS,TC and TG levels(r=0.672,0.587,0.511 and 0.423;all P＜0.05).The ROC curve graph showed that the area under the curve was 0.919,with sensitivity and specificity of 85.11％and 89.36％,respectively.Compared with the NG group,the HG group showed a significant increase in cell apoptosis rate and the pro-tein expressions of cleaved caspase-3,Bax,TNF-a,IL-6,p-IκBa and p-p65(all P＜0.05);compared with the HG+anti-miR-NC group,the HG+anti-miR-3197 group showed a significant decrease in cell apoptosis rate and the protein expres-sions of cleaved caspase-3,Bax,TNF-a,IL-6,p-IκBa and p-p65(allP＜0.05).Conclusion The miR-3197 is highly ex-pressed in the peripheral blood of DR patients and high glucose-induced hRMECs.Down-regulation of miR-3197 can allevi-ate high glucose-induced hRMEC apoptosis and inflammatory injury,and its mechanism of action may be related to the inhi-bition of the NF-κB signaling pathway.
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Objective To investigate the expression of circular ribonucleic acid carnitine palmitoyltrans-ferase 1A(circRNA CPT1A)in patients with diabetic retinopathy(DR)and its mechanism of action on neuropathy.Methods To-tally 80 patients(102 eyes)with type 2 diabetes admitted to our hospital from January 2019 to January 2022 were selected,including 22 patients(28 eyes)with no DR(NDR group),38 patients(48 eyes)with non-proliferative DR(NPDR group),and 20 patients(26 eyes)with proliferative DR(PDR group).Optical coherence tomography angiography was used to measure the thickness of the peripapillary retinal nerve fiber layer(pRNFL)and macular ganglion cell complex(GCC),the level of phosphatase and tensin homolog(PTEN)in peripheral blood was detected by Western blot,and the circRNA CPT1A level in peripheral blood was detected by fluorescence quantitative polymerase chain reaction.The levels of circRNA CPT1A and PTEN in peripheral blood,as well as the thickness of pRNFL and GCC,were compared among three groups,and Pearson correlation analysis was used to investigate the correlation between circRNA CPT1A and PTEN,pRNFL and GCC thickness.Results The circRNA CPT1A in the peripheral blood of the PDR group was higher than that in the NDR group and NPDR group;the PTEN in the peripheral blood of the PDR group was lower than that in the NDR group and NP-DR group(all P＜0.05).There was no statistically significant difference in the expression of circRNA CPT1A and PTEN be-tween NDPR group and NDR group(all P＞0.05).The Pearson correlation analysis showed that the expression level of cir-cRNA CPT1A in peripheral blood was negatively correlated with PTEN(P＜0.05).With the increase in disease severity,the thickness of pRNFL and GCC showed a decreasing trend;the thickness of pRNFL and GCC in the whole,upper and lower parts of eyes in the NDR group were higher than those in the NPDR group(all P＜0.05),while those in the NPDR group were higher than the PDR group(all P＜0.05).Pearson correlation analysis showed that the expression level of cir-cRNA CPT1A in peripheral blood was negatively correlated with the thickness of pRNFL and GCC in the whole,upper and lower parts of the observed eyes(all P＜0.05).Conclusion With the increase in the severity of DR,circRNA CPT1A in the peripheral blood of DR patients shows an increasing trend and is negatively correlated with peripheral blood PTEN lev-el,as well as macular pRNFL and GCC thickness.The mechanism of action may be that circRNA CPT1A negatively regu-lates the expression of PTEN and thus participates in the occurrence and development of DR.
ABSTRACT
Diabetic retinopathy,a main microvascular complication of diabetes,remains the leading cause of blindness in the working-age population,but its specific pathogenesis has not been fully elucidated.microRNAs(miRNAs)are small non-coding RNAs,acting as post-transcriptional regulators of gene expression.Its aberrant expression plays a key role in modulating pathological processes associated to many diseases.Studies confirmed the role of miRNAs in the regulation of oxidative stress,inflammation,cell death and angiogenesis which influences the development of DR.This review focuses on the role of miRNAs in DR,which may provide a reference basis for diagnosis,prognosis and therapeutics.
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Objective To explore the changes in the expression of glucose transporters 1/4(GLUT1/4)and Sirtuins in the retina of rats with diabetes.Methods Twenty 8-week-old healthy male Sprague-Dawley rats were randomly divid-ed into normal control and diabetic groups.Rats in the diabetic group received a disposable intraperitoneal injection of 60 mg·kg-1 streptozotocin to induce the diabetes model,while rats in the normal control group were injected with an equiva-lent amount of solvent.Body weight and blood glucose were measured at 2-week intervals.At 12 weeks after modeling,color Doppler ultrasound was applied to detect blood flow parameters in the central retinal artery(CRA)of rats;after an-esthetizing rats with sodium pentobarbital,eyeballs were harvested,and the pathological changes of rat retinal tissue were observed by hematoxylin & eosin(HE)staining.The expression of messenger ribonucleic acid(mRNA)for GLUT 1/4 and Sirtuins in the retina of rats were detected by immunohistochemical staining,Western blot and quantitative of reverse tran-scription polymerase chain reaction(qRT-PCR),respectively.Results At 12 weeks after modeling,compared with the normal control group,peak systolic velocity and end diastolic velocity were significantly lower in CRA of rats in the diabetic group(both P＜0.001);there were no significant differences in resistance index and pulsatility index(both P＞0.05).The HE staining results at 12 weeks after modeling showed that rats in the normal control group had clear structure in each layer of retinal tissues,closely and regularly arranged cells,and no obvious pathological changes;rats in the diabetic group showed decreased retinal thickness,blurred boundary of each layer,disordered structure and reduced cell number.Immu-nohistochemical staining at 12 weeks after modeling showed that GLUT 1 was mainly located in the retinal pigment epithelial layer of rats,and GLUT 4 was located in the ganglion cell layer,inner plexiform layer and photoreceptor layer.Western blot results showed that the relative expression of GLUT1 and GLUT 4 protein in the diabetic group were lower than that in the normal control group(both P＜0.05),and the relative expression of SIRT1-SIRT7 protein in the retina of rats in the di-abetic group were lower than those of the normal control group(all P＜0.05).qRT-PCR showed a decreased relative ex-pression of SIRT1-SIRT7 mRNA in the retina of rats in the diabetic group compared with that of the normal control group(allP＜0.01).Conclusion Diabetes can cause altered expression of GLUT1/4 and Sirtuins in the retinal tissue of rats,and GLUT1/4 and Sirtuins may be involved in the occurrence and development of diabetic retinopathy.
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Objective To investigate the detection rate and grading diagnostic value of ultra-wide field swept-source optical coherence tomography angiography(UWF SS-OCTA)combined with ultra-wide field scanning laser ophthalmoscopy(UWF SLO)in diabetic retinopathy(DR)lesions.Methods In this cross-sectional study,diabetic patients attending the Ophthalmology Department of Sichuan Provincial Peoples Hospital were recruited.All participants underwent UWF SS-OC-TA,UWF SLO and fundus fluorescein angiography to detect DR lesions,including microaneurysms(MA),intraretinal hem-orrhages(IRH),nonperfusion areas(NPAs),intraretinal microvascular abnormalities(IRMAs),venous beading(VB),neovascularization elsewhere(NVE),neovascularization of the optic disc(NVD),and vitreous hemorrhage(VH).The re-sults of the combination of three imaging examinations(triple imaging)were used as the standards,evaluating the detec-tion rate and severity grading consistency in DR lesions of pairwise combinations of different imaging modalities.Results A total of 101 patients(175 eyes)were included.Compared with the triple imaging results,the detection rates of UWF SS-OCTA combined with UWF SLO for MA,IRH,NPAs,IRMAs,NVE,NVD and VH were 91％,83％,77％,69％,27％,10％and 12％,respectively,with Kappa values of 0.812,1.000,1.000,1.000,0.986,0.970 and 1.000.Compared with the triple imaging results,the combination of UWF SS-OCTA and UWF SLO demonstrated excellent consistency in grading the severity of DR(Kappa=0.943).Conclusion UWF SS-OCTA combined with UWF SLO can accurately identify MA,IRH,NPAs,IRMAs,NVE,NVD and VH,demonstrating high accuracy in DR screening and grading diagnosis,making it suitable for large-scale screening and management of DR in clinical practice.
ABSTRACT
Diabetic retinopathy(DR)is one of the most common fundus vascular diseases and a leading cause of blindness in adults of working age.The occurrence and development of DR involves a variety of pathophysiologic mecha-nisms,including metabolic dysregulation,oxidative stress,inflammation,and neurovascular unit hypofunction.Conven-tional clinical treatments,such as anti-vascular endothelial growth factor drugs and retinal laser photocoagulation,have long treatment cycles and variable outcomes in some patients and sometimes require vitrectomy in the later stages of the disease.With the in-depth research on the molecular level of the pathogenesis of DR,a number of biological therapeutic modalities,such as targeted therapy,gene therapy,immunotherapy and cell therapy,have received more and more atten-tion from researchers.This review summarizes the biologic therapeutic modalities currently available for DR and outlines the benefits and limitations of these approaches with a view to informing researchers.