Risk factors associated with retinal neovascularization of diabetic retinopathy in type 2 diabetes mellitus

AIM: To evaluate the risk factors associated with retinal neovascularization of diabetic retinopathy in northern Chinese Han patients with type 2 diabetes mellitus (T2DM). METHODS: The clinical characteristics of 200 patients with proliferative diabetic retinopathy (PDR) and 100 age-matched healthy individuals were compared. The univariate and multivariate logistic regression analysis were performed in the patients with PDR. RESULTS: Fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), uric acid (UA), white blood cell count (WBC), absolute neutrophil count, hematocrit (HCT) and mean platelet volume (MPV) and mean platelet volume (MPV) were all significantly higher in patients with PDR than in the control group (P<0.05). The univariate and multivariate logistic regression analysis showed that risk factors independently associated with retinal neovascularization of DR were duration of diabetes mellitus (OR=1.112; P=0.000), BUN (OR=1.277; P=0.000), smoking (OR=3.967; P=0.000) and MPV (OR=2.472; P=0.000). On the other hand, panretinal photocoagulation was associated with reduced risk of retinal neovascularization (OR=0.983; P=0.000). CONCLUSION: Preventing and controlling T2DM in terms of risk factors, including duration of diabetes, BUN, smoking and MPV, might offer novel approaches to prevent or delay the onset of retinal neovascularization in patients with PDR.

Effects of nuclear factor κB expression on retinal neovascularization and apoptosis in a diabetic retinopathy rat model

AIM: To investigate the expression and role of nuclear factor κB(NF-κB) in diabetic retinopathy(DR) and its relationship with neovascularization and retinal cell apoptosis. METHODS: A total of 80 male Wistar rats were randomly assigned to control(4, 8, 12 and 16 wk, n =10 in each group) and diabetes mellitus(DM) groups(4, 8, 12 and 16wk, n =10 in each group). A diabetic rat model was established by intraperitoneal injection of streptozotocin(60 mg/kg). After 4, 8, 12 and 16 wk, rats were sacrificed.Retinal layers and retinal neovascularization growth were stained with hematoxylin-eosin and examined under light microscopy. Cell apoptosis in the retina was detected by Td T-mediated d UTP nick end labeling, and NF-κB distribution and expression in the retina was determined using immunohistochemistry. RESULTS: DM model success rate up to 100%.Diabetes model at each time point after the experimental groupcompared with the control group, the blood glucose was significantly increased, decreased body weight, each time point showed significant differences compared with the control group(P 【0.01). After 12 wk other pathological changes in the retina of diabetic rats were observed; after 16 wk, neovascularization were observed. After 1mo, retinal cell apoptosis was observed.Compared with the control group, NF-κB expression in the DM group significantly increased with disease duration.CONCLUSION: With the prolonging of DM progression,the expression NF-κB increases. NF-κB may be related to retinal cell apoptosis and neovascularization.

Inhibitory effect of maspinon neovascularization in diabetic retinopathy

BACKGROUND Diabetic retinopathy(DR)is a serious and potentially blinding complication of diabetes mellitus.Retinal neovascularization is one of the main pathological features of proliferative DR,and inhibiting retinal neovascularization is a research focus.AIM The aim was to evaluate the effect of intravitreal injection of recombinant human maspin on neovascularization in DR.METHODS An oxygen-induced retinopathy(OIR)mouse model was used to simulate neovascularization in DR.New born C57BL/6J mice were randomly divided to a normal control group,a maspin injection OIR group,and an OIR group.The mice in the maspin injection OIR group were injected with recombinant human maspin in the bilateral vitreous cavity on postnatal day P12,and those in the OIR group were injected with sterile phosphate buffered saline.The protein expression of vascular endothelial growth factor(VEGF)and hypoxia-inducible factor 1-alpha(HIF-1α)in the retina was measured by western blotting,and the mRNA expression of VEGF and HIF-1αwas measured by real-time polymerase chain reaction.The vascular cell nuclei that broke through the inner limiting membrane(ILM)were counted in haematoxylin-eosin stained retinal sections.RESULTS It was found that the number of vascular cell nuclei breaking through the ILM was 31.8±8.75 in the OIR group,which was significantly more than that in the normal control group(P<0.001).The number of vascular cell nuclei breaking through the ILM was 6.19±2.91 in the maspin injection OIR group,which was significantly less than that in OIR group(P<0.01).The relative protein and mRNA expression of VEGF and HIF-1αwas significantly lower in the retinas in the maspin injection OIR group than in those in the OIR group(P<0.01).CONCLUSION Maspin inhibited neovascularization in DR by modulating the HIF-1α/VEGF pathway,which provides a potential and effective strategy for the treatment of DR.

Construction and validation of a neovascular glaucoma nomogram in patients with diabetic retinopathy after pars plana vitrectomy

BACKGROUND Neovascular glaucoma(NVG)is likely to occur after pars plana vitrectomy(PPV)for diabetic retinopathy(DR)in some patients,thus reducing the expected benefit.Understanding the risk factors for NVG occurrence and building effective risk prediction models are currently required for clinical research.AIM To develop a visual risk profile model to explore factors influencing DR after surgery.METHODS We retrospectively selected 151 patients with DR undergoing PPV.The patients were divided into the NVG(NVG occurrence)and No-NVG(No NVG occurrence)groups according to the occurrence of NVG within 6 months after surgery.Independent risk factors for postoperative NVG were screened by logistic regression.A nomogram prediction model was established using R software,and the model’s prediction accuracy was verified internally and externally,involving the receiver operator characteristic curve and correction curve.RESULTS After importing the data into a logistic regression model,we concluded that a posterior capsular defect,preoperative vascular endothelial growth factor≥302.90 pg/mL,glycosylated hemoglobin≥9.05%,aqueous fluid interleukin 6(IL-6)≥53.27 pg/mL,and aqueous fluid IL-10≥9.11 pg/mL were independent risk factors for postoperative NVG in patients with DR(P<0.05).A nomogram model was established based on the aforementioned independent risk factors,and a computer simulation repeated sampling method was used to internally and externally verify the nomogram model.The area under the curve(AUC),sensitivity,and specificity of the model were 0.962[95%confidence interval(95%CI):0.932-0.991],91.5%,and 82.3%,respectively.The AUC,sensitivity,and specificity of the external validation were 0.878(95%CI:0.746-0.982),66.7%,and 95.7%,respectively.CONCLUSION A nomogram constructed based on the risk factors for postoperative NVG in patients with DR has a high prediction accuracy.This study can help formulate relevant preventive and treatment measures.

Panretinal photocoagulation versus panretinal photocoagulation plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy

AIM： To evaluate the effects of panretinal photocoagulation （PRP） compared with PRP plus intravitreal bevacizumab （IVB） in patients with high-risk proliferative diabetic retinopathy （PDR） according to the Early Treatment Diabetic Retinopathy Study criteria.METHODS： The data were collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. After treated with standard PRP, the eyes were randomly assigned to receive only PRP （PRP group） or PRP plus intravitreal injection of 1.25 mg of bevacizumab （PRP-Plus group）. Patients underwent complete ophthalmic evaluation, including best corrected visual acuity （BCVA）, intraocular pressure （IOP）, and new vessel size in fluorescein angiography （FA） and optical coherence tomography for the assessment of central subfield macular thickness （CSMT） at baseline and at weeks 12 （±2）, 16 （±2）, 24 （±2） and 48 （±2）. Main outcome measures also included vitreous clear-up time and neovascularization on the disc （NVD） regression time. Adverse events associated with intravitreal injection were investigated.RESULTS： Thirty consecutive patients （n=36 eyes） completed the 48-week follow-up. There was no significant difference between the PRP and PRP-Plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active neovascularizations （NVs）, BCVA or CSMT at baseline. The mean vitreous clear-up time was 12.1±3.4wk after PRP and 8.4±3.5wk after PRP combined with IVB. The mean time interval from treatment to complete NVD regression on FA examination was 15.2±3.5wk in PRP group and 12.5±3.1wk in PRP-Plus group. No significant difference in CSMT was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-Plus group compared with the PRP group （P〈0.05）. Patients received an average of 1.3 injections （range： 1-2）. Ten eyes （27.8%） underwent 2 injections. Two eyes had ocular complication of PDR progression to dense vitreous hemorrhage （VH）. No major adverse events were identified.CONCLUSION： The adjunctive use of IVB with PRP is associated with a greater reduction in the area of active leaking NVs than PRP alone in patients with high-risk PDR. Short-term results suggest combined IVB and PRP achieved rapid clearance of VH and regression of retinal NV in the treatment of high-risk PDR. Further studies are needed to determine the effect of repeated intravitreal bevacizumab injections and the proper number of bevacizumab injections as an adjuvant.

Ahmed valve implantation for neovascular glaucoma after 23-gauge vitrectomy in eyes with proliferative diabetic retinopathy

·AIM: To report on the outcome of Ahmed glaucoma valve (AGV) implantation for the management of neovascular glaucoma (NVG) after 23 -gauge vitrectomy for proliferative diabetic retinopathy (PDR). ·METHODS: Twelve medically uncontrolled NVG with earlier 23 -gauge vitrectomy for PDR underwent AGV implantation. The control of intraocular pressure (IOP), preoperative and postoperative best -corrected visual acuity, the development of intraoperative and postoperative complications were evaluated during the follow-up. ·RESULTS: The mean follow-up was 15.4±4.3 months (9-23 months). Mean preoperative IOP was 49.4±5.1mmHg and mean postoperative IOP at the last visit was 17.5 ± 1.6mmHg. The control of IOP was achieved at the final follow -up visits in all patients, however, 8 of 12 patients still needed anti-glaucoma medication (mean number of medications, 0.8±0.7). The visual acuity improved in nine eyes, and the visual acuity unchanged in three eyes at the final follow -up visits. The complications that occurred were minor hyphema in three eyes, choroid detachment in two eyes, and the minor hyphema and choroid detachments were reabsorbed without any surgical intervention. ·CONCLUSION: AGV implantation is a safe and effective procedure that enables successful IOP control and vision preservation in the NVG patients with the history of earlier 23-gauge vitrectomy for PDR.·

Phosphorylation of alphaB-crystallin in epiretinal membrane of human proliferative diabetic retinopathy

AIMTo examine phosphorylation of alphaB-crystallin (p-&#x003b1;BC), a vascular endothelial growth factor (VEGF) chaperone, and immunohistochemically investigate relationship between p-&#x003b1;BC, VEGF and phosphorylated p38-mitogen-activated protein kinase (p-p38 MAPK) in the epiretinal membrane of human proliferative diabetic retinopathy (PDR).METHODSEleven epiretinal membranes of PDR surgically excised were included in this study. Two normal retinas were also collected from enucleation tissues due to choroidal melanoma. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with anti-p-&#x003b1;BC, VEGF, CD31, and p-p38 MAPK antibodies.RESULTSImmunoreactivity for p-&#x003b1;BC was observed in all of the epiretinal membranes examined, where phosphorylation on serine (Ser) 59 showed strongest immunoreactivity in over 70% of the membranes. The immunolocalization of p-&#x003b1;BC was detected in the CD31-positive endothelial cells, and co-localized with VEGF and p-p38 MAPK in PDR membranes. Immunoreactivity for p-&#x003b1;BC, however, was undetectable in endothelial cells of the normal retinas, where p-p38 MAPK immunoreactivity was less marked than PDR membranes.CONCLUSIONPhosphorylation of &#x003b1;BC, in particular, phosphorylation on Ser59 by p-p38 MAPK may play a potential role as a molecular chaperon for VEGF in the pathogenesis of epiretinal membranes in PDR.

Klotho:A new therapeutic target in diabetic retinopathy?

Klotho(Kl)is considered an antiaging gene,mainly for the inhibition of the insulin-like growth factor-1 signaling.Kl exists as full-length transmembrane,which acts as co-receptor for fibroblast growth factor receptor,and in soluble forms(sKl).The sKl may exert pleiotropic effects on organs and tissues by regulating several pathways involved in the pathogenesis of diseases associated with oxidative and inflammatory state.In diabetic Patients,serum levels of Kl are significantly decreased compared to healthy subjects,and are related to duration of diabetes.In diabetic retinopathy(DR),one of the most common microvascular complications of type 2 diabetes,serum Kl levels are negatively correlated with progression of the disease.A lot of evidences showed that Kl regulates several mechanisms involved in maintaining homeostasis and functions of retinal cells,including phagocytosis,calcium signaling,secretion of vascular endothelial growth factor A(VEGF-A),maintenance of redox status,and melanin biosynthesis.Experimental data have been shown that Kl exerts positive effects on several mechanisms involved in onset and progression of DR.In particular,treatment with Kl:(1)Prevents apoptosis induced by oxidative stress in human retinal endothelial cells and in retinal pigment epithelium(RPE)cells;(2)reduces secretion of VEGF-A by RPE cells;and(3)decreases subretinal fibrosis and preserves autophagic activity.Therefore,Kl may become a novel biomarker and a good candidate for the treatment of DR.

Clinical efficacy of Ahmed glaucoma valve implantation combined with 23-gauge vitrectomy for medically uncontrolled neovascular glaucoma with proliferative diabetic retinopathy

AIM:To describe the clinical results of combined Ahmed valve implantation and 23-gauge vitrectomy for medically uncontrolled neovascular glaucoma(NVG)secondary to proliferative diabetic retinopathy(PDR).METHODS:The medical records of medically uncontrolled NVG patients with PDR who underwent Ahmed valve implantation and 23-gauge vitrectomy between March 2016 and December 2018 were reviewed.Enrolled patients had at least 6-month follow-up.Panretinal photocoagulation(PRP),anti-vascular endothelial growth factor,surgery and medication history were documented.RESULTS:Eleven eyes of 11 patients were included in our study.The visual acuity improved in 8 eyes and remained unchanged in 3 eyes.The preoperative intraocular pressure(IOP)was significantly decreased at the last follow-up(48.8±4.3 to 17.0±1.5 mm Hg,P<0.001).All eyes needed three topical anti-glaucomatous medications before surgery,but the number was significantly reduced to 0.72±0.19 at the last visit(P<0.001).Four eyes had choroidal detachment and 3 eyes had minor hyphemia,all of which gradually resolved without treatments in one week.CONCLUSION:Ahmed glaucoma valve implantation combined with 23-gauge vitrectomy might be a safe and alternative treatment for NVG with PDR.

Intravitreal aflibercept for rubeosis iridis secondary to proliferative diabetic retinopathy

The purpose of this article is to report a case with rubeosis iridis treated by intravitreal aflibercept. A 61-year-old man had iris neovascularization and scanty vitreous hemorrhage secondary to proliferative diabetic retinopathy in the right eye. Neither neovascularization of angle nor elevation of intraocular pressure was found. Single intravitreal al ibercept 2 mg injection was performed. Rubeosis iridis disappeared on the next day. Scattered retinal laser photocoagulation was added 1 week later. There was no recurrence after 3-month follow-up. Aflibercept may serve as another anti-vascular endothelial growth factor(anti-VEGF) for treating rubeosis iridis.

Blueberry anthocyanins extract attenuates oxidative stress and angiogenesis on an in vitro high glucose-induced retinopathy model through the miR-33/GLCCI1 axis

Background:Diabetes retinopathy(DR)is a complication of diabetes that affects patients’vision.Previous studies have found blueberry anthocyanins extract(BAE)can inhibit the progression of DR,but its mechanism is not completely clear.Methods:To study the role of BAE in diabetes retinopathy,we treated human retinal endothelial cells(HRCECs)with 30 mM high glucose to simulate the microenvironment of diabetes retinopathy and used BAE to intervene the in vitro high glucose-induced retinopathy model.HRCEC cell viability and apoptosis rates were examined by Cell Counting Kit 8(CCK-8)assay and flow cytometry assay.The binding sites between miR-33 and glucocorticoid-induced transcript 1(GLCCI1)were assessed by luciferase reporter assay.Retinal neovascularization and oxidative stress contribute to diabetic retinopathy.The tubule formation assay was applied to detect the retinal neovascularization.The oxidative stress in the HRCECs was manifested by the reactive oxygen species(ROS)level,the malondialdehyde(MDA)level,and the superoxide dismutase(SOD)activity.Results:Compared with HRCECs cells cultured under normal conditions,high glucose(HG)can induce oxidative stress in HRCRCs,specifically manifested in the increase of ROS and MDA levels,and the decrease of SOD activity.BAE relieved the tubule formation in n the HRCEC.BAE also relieved the ROS and MDA levels and increased the SOD activity.Luciferase reporter assay revealed that GLCCI1 is a target molecule downstream of miR-33.In HRCEC,BAE significantly inhibited the expression of miR-33 induced by HG.miR-33 mimic inhibited the BAE’s effects on oxidative stress and angiogenesis in an in vitro high glucose-induced retinopathy model.Conclusion:BAE alleviated the oxidative stress and microangiogenesis of HRCEC by regulating the miR-33/GLCCI1 axis.

Chinese Medicines in Diabetic Retinopathy Therapies

Diabetic retinopathy(DR),a chronic microvascular retinal disorder leading to retinal nonperfusion and ischemia,is one of the leading causes of blindness among individuals of working age.In?ammation and neovascularization play important roles in the development of DR,especially proliferative DR(PDR).Therapies with Chinese medicines(CMs) that improve microcirculation complementary to conventional treatments increase the chances of delaying PDR development and improving visual acuity in diabetes patients.This review aimed to introduce promising CMs targeting DR patients in clinical practice,together with their underlying molecular mechanisms.

Expression and role of P-element-induced wimpy testis-interacting RNA in diabetic-retinopathy in mice

BACKGROUND As one of the major microvascular complications of diabetes,diabetic retinopathy(DR)is the leading cause of blindness in the working age population.Because the extremely complex pathogenesis of DR has not been fully clarified,the occurrence and development of DR is closely related to tissue ischemia and hypoxia and neovascularization The formation of retinal neovascularization(RNV)has great harm to the visual acuity of patients.AIM To investigate the expression of P-element-induced wimpy testis-interacting RNA(piRNA)in proliferative DR mice and select piRNA related to RNV.METHODS One hundred healthy C57BL/6J mice were randomly divided into a normal group as control group(CG)and proliferative DR(PDR)group as experimental group(EG),with 50 mice in each group.Samples were collected from both groups at the same time,and the lesions of mice were evaluated by hematoxylin and eosin staining and retinal blood vessel staining.The retinal tissues were collected for second-generation high-throughput sequencing,and the differentially expressed piRNA between the CG and EG was detected,and polymerase chain reaction(PCR)was conducted for verification.The differentially obtained piRNA target genes and expression profiles were enrichment analysis based on gene annotation(Gene Ontology)and Kyoto Encyclopedia of Genes and Genomes.RESULTS In the CG there was no perfusion area,neovascularization and endothelial nucleus broke through the inner boundary membrane of retinap.In the EG,there were a lot of nonperfused areas,new blood vessels and endothelial nuclei breaking through the inner boundary membrane of the retina.There was a statistically significant difference in the number of vascular endothelial nuclei breaking through the inner retinal membrane between the two groups.High-throughput sequencing analysis showed that compared with the CG,a total of 79 piRNAs were differentially expressed in EG,among which 43 piRNAs were up-regulated and 36 piRNAs were down-regulated.Bioinformatics analysis showed that the differentially expressed piRNAs were mainly concentrated in the signaling pathways of angiogenesis and cell proliferation.Ten piRNAs were selected for PCR,and the results showed that the expression of piR-MMU-40373735,piRMMU-61121420,piR-MMU-55687822,piR-MMU-1373887 were high,and the expression of piR-MMU-7401535,piR-MMU-4773779,piR-MMU-1304999,and piR-MMU-5160126 were low,which were consistent with the sequencing results.CONCLUSION In the EG,the abnormal expression of piRNA is involved in the pathway of angiogenesis and cell proliferation,suggesting that piRNAs have some regulatory function in proliferative diabetic-retinopathy.

Effect of periocular injection of celecoxib and propranolol on ocular level of vascular endothelial growth factor in a diabetic mouse model

AIM： To investigate the effects of periocular injection of propranolol and celecoxib on ocular levels of vascular endothelial growth factor （VEGF） in a diabetic mouse model. METHODS： Forty 4-6wk BALB-C male mice weighing 20-25 g were used. The study groups included： nondiabetic control （group 1）, diabetic control （group 2）, diabetic propranolol （group 3）, and diabetic celecoxib （group 4）. After induction of type 1 diabetes by streptozotocin, propranolol （10 μg） and celecoxib （200 μg dissolved in carboxymethylcellulose 0.5%） were injected periocularly. The ocular level of VEGF was measured in all the study groups using enzyme-linked immuno sorbent assay （ELISA） method. RESULTS： Ocular VEGF level was significantly increased （1.25 fold） in the diabetic control group when compared to the non-diabetic group one week after induction with streptozotocin （P=0.002）. Both periocular propranolol and celecoxib significantly reduced ocular VEGF levels （P=0.047 and P〈0.001, respectively）. The effect was more pronounced with celecoxib, CONCLUSION： The periocular administration of propranolol and celecoxib can significantly reduce ocular VEGF levels in a diabetic mouse model.

抗VEGF药物联合全视网膜光凝治疗糖尿病视网膜病变的效果和预后分析

目的探讨抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物联合全视网膜光凝(panretinal photocoagulation,PRP)治疗糖尿病视网膜病变的效果和预后分析。方法选取三明市第二医院2020年1月—2023年1月收治的50例糖尿病视网膜病变者(78眼),以随机数字表法分为2组,各25例(39眼)。对照组患者给予PRP治疗,研究组给予抗VEGF药物联合PRP治疗。比较2组术前、术后恢复指标,统计患者治疗后的不良反应,评价治疗效果。结果术后,2组最佳矫正视力(best correct vision acuity,BCVA)优于术前,视网膜新生血管(retinal neovascularization,RNV)面积、中央视网膜厚度(central retinal thickness,CRT)低于术前,且研究组BCVA高于对照组;RNV面积、CRT低于对照组,差异有统计学意义(P<0.05);研究组并发症总发生率为5.13%,低于对照组的23.08%,差异有统计学意义(P<0.05);研究组治疗总有效率为94.97%,高于对照组的79.49%,差异有统计学意义(P<0.05)。结论糖尿病视网膜病变以抗VEGF药物联合PRP治疗可改善术后BCVA,减少RNV面积、CRT,降低并发症发生率,提升治疗效果。

Diverse roles of macrophages in intraocular neovasculardiseases:a review

Macrophages are involved in angiogenesis, and might also contribute to the pathogenesis of intraocular neovascular diseases. Recent studies indicated that macrophages exert different functions in the process of intraocular neovascularization, and the polarization of M1 and M2 phenotypes plays extremely essential roles in the diverse functions of macrophages. Moreover, a large number of cytokines released by macrophages not only participate in macrophage polarization, but also associate with retinal and choroidal neovascular diseases. Therefore, macrophage might be considered as a novel therapeutic target to the treatment of pathological neovascularization in the eye. This review mainly summarizes diverse roles of macrophages and discusses the possible mechanisms in retinal and choroidal neovascularization.

The roles of macrophage migration inhibitory factor in retinal diseases

Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive immunity.There are some evidences that MIF is involved in many vitreoretinal diseases.For example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis treatment.MIF also alleviates trauma-induced and glaucoma-induced optic nerve damage.Furthermore,MIF is critical for retinal/choroidal neovascularization,especially complex neovascularization.MIF exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal degeneration.MIF protects uveal melanoma from attacks by natural killer cells.The mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt pathway.MIF also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling pathway.This review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma.

金合欢素调节Hippo信号通路对糖尿病视网膜病变大鼠血管生成的影响

目的探究金合欢素(Aca)调节Hippo信号通路对糖尿病视网膜病变(DR)大鼠血管生成的影响。方法将60只SD大鼠随机分为对照组、DR组、Aca低剂量组(10 mg/kg)、Aca中剂量组(20 mg/kg)、Aca高剂量组(30 mg/kg)、Hippo-yes相关蛋白(YAP)通路抑制剂Verteporfin组(Aca高剂量30 mg/kg+Verteporfin 0.8 pmol/kg),每组10只。除对照组外,采用链脲佐菌素和高脂饲料喂养构建DR模型,检测大鼠体质量和空腹血糖(FBG)水平,荧光素血管造影(FFA)观察视网膜血管新生和荧光素渗漏,酶联免疫吸附试验检测血清血管内皮生长因子(VEGF)、促血管生成素-2(Ang-2)水平,苏木素伊红染色观察视网膜组织病理形态变化,Western blot法检测VEGF、缺氧诱导因子1α(HIF-1α)、血管细胞黏附分子-1(VCAM-1)及Hippo信号通路蛋白表达。结果与对照组比较,DR组大鼠视网膜细胞排列混乱、松散,新生血管形成,大量荧光素渗漏,体质量、大肿瘤抑制激酶2(LATS2)、磷酸化YAP(p-YAP)表达降低,FBG、VEGF、Ang-2、HIF-1α、VCAM-1、YAP、转录调节因子(TAZ)、TEA结构域家族成员1(TEAD1)表达增加(P<0.05);与DR组比较,Aca低、中、高剂量组和Verteporfin组大鼠视网膜细胞排列整齐,新生血管形成和荧光素渗漏减少,体质量、LATS2、p-YAP表达增加,FBG、VEGF、Ang-2、HIF-1α、VCAM-1、YAP、TAZ、TEAD1表达降低(P<0.05),高剂量组效果更明显,但Verteporfin组与Aca高剂量组对DR大鼠各指标的作用效果差异无统计学意义。结论Aca能抑制DR大鼠血管生成,改善视网膜病理损伤,其作用机制可能与调节Hippo信号通路有关。

高速扫频源光学相干断层血流成像不同扫描宽度对糖尿病视网膜病变病灶检测率的影响

目的探讨高速扫频源光学相干断层扫描血流成像(SS-OCTA)不同扫描宽度对糖尿病视网膜病变(DR)病灶检测率的影响。方法纳入2021年10月至2023年10月于四川省人民医院眼科就诊的糖尿病(DM)患者126例213眼,接受包括24 mm×20 mm高速广域SS-OCTA扫描方案在内的全面眼科检查。从24 mm×20 mm的OCTA图像中提取一个中心区域记为“12 mm×12 mm中心区”,其余区域记为“12~24 mm环区”。记录并比较使用不同扫描区域的DR病灶检测率。结果共纳入126例参与者的213只眼(54只眼糖尿病无DR,53只眼轻度至中度非增殖性糖尿病视网膜病变(NPDR),54只眼重度NPDR,52只眼增殖性糖尿病视网膜病变(PDR))。24 mm×20 mm OCTA图像无灌注区(NP)检测率显著高于12 mm×12 mm中心区(P<0.05);12~24 mm环区的缺血指数(ISI)中位数明显高于12 mm×12 mm中心区(P<0.05);7眼视网膜新生血管(NV),10眼视网膜内微血管异常(IRMA)病变仅存在于12~24 mm环区域。结论高速广域SS-OCTA单次扫描可捕获24 mm×20 mm视网膜血管图像,更宽的扫描范围可以提高视网膜缺血程度检测的准确性和NV、IRMA的检测率。

富组氨酸糖蛋白在大鼠糖尿病视网膜病变新生血管形成中的作用

目的:探讨富组氨酸糖蛋白(HRG)在大鼠糖尿病视网膜病变新生血管形成中的作用。方法:建立链脲佐菌素(STZ)诱导的SD大鼠糖尿病模型,蛋白免疫印迹法(WB)检测正常(WT)组、糖尿病(DM)组视网膜中HRG、血管生成因子(VEGF)的蛋白表达情况。转染HRG小干扰RNA低表达序列,WB验证在高糖诱导的人视网膜微血管内皮细胞(hRMECs)中HRG的蛋白表达情况,选择最佳si-HRG#298序列用于后续实验。动物实验通过腺相关病毒载体沉默HRG,玻璃体腔注射HRG空载体对照组(AAV2-sh-NC)及HRG基因沉默组(AAV2-sh-HRG#298),WB验证HRG的蛋白表达情况后,通过HE染色观察各组视网膜结构变化,PAS染色观察各组视网膜新生血管变化情况,WB检测各组HRG及VEGF的蛋白表达情况。结果:HE染色发现DM组大鼠视网膜结构出现紊乱,神经节细胞层细胞数量减少,内核层和外核层细胞数量减少,视网膜总厚度也减少(P<0.05);PAS染色观察DM组大鼠视网膜中无细胞毛细血管明显增多(P<0.05);DM组大鼠视网膜中HRG及血管生成因子VEGF的蛋白表达上调(P<0.05);高糖诱导的hRMECs中转染HRG后其蛋白表达明显下调(P<0.05);HRG基因沉默可以抑制糖尿病视网膜的新生血管形成,下调VEGF的蛋白表达(P<0.05)。结论:HRG促进糖尿病大鼠视网膜的新生血管形成,HRG基因沉默可以抑制其新生血管形成。