Expression of cyclinD1 in a rat model of oxygen-induced retinopathy

This study sought to elucidate the correlation between cyclinD1 expression and the emergence of neovascularization in oxygen-induced retinopathy （OIR）. OIR was induced in Sprague-Dawley 7-day-old neonatal rats exposed to hyperoxia （75% O2） for 5 days, and then returned to room air. Adenosine diphosphatase staining showed that the neovascularization started to emerge at rat age of day 14, and reached a peak at day 17, then gradually decreased and resolved by day 26. Immunohistochemical and immunofluorescence staining revealed that cyclinD1 protein expression was seen in the OIR rats at the age of day 12, then gradually increased and returned to normal levels by day 26. These experimental findings demonstrated that the temporal pattern of cyclinD1 protein expression is consistent with the emergence of retinal neovascularization.

Role of unc5b in retinal neovascularization in mice with oxygen-induced retinopathy

AIM: To explore the role of unc5b in retinal neovascularization in murine oxygen-induced retinopathy (OIR). METHODS: On postnatal 7 (P7), C57BL/6J mice were exposed to 75% +/- 2% oxygen for 5 days. On postnatal 12 (P12), the mice were brought back to the room air (21% oxygen) to induce retinal neovascularization. Western blot analysis was performed to examine the temporal expression of unc5b in murine retinas. Double staining for unc5b and isolectin B4 were employed to determine the location of unc5b in murine retinas. The effect of unc5b on retinal neovascularization was evaluated by intravitreal injection of unc5b-FC in mice with OIR. Retinal neovascularization was measured by counting neovascular cell nuclei above the internal limiting membrane and by angiography of flat-mounted retinas perfused with fluorescein dextran. o RESULTS: Compared to age-matched normal mice, the expression of unc5b was significantly increased in retinas of OIR mice on P17 and P21. Unc5b was apparently expressed in retinal vessels of OIR while being negative in normal retinal vessels. Retinal neovascularization in eyes injected with unc5b-FC was significantly reduced. CONCLUSION: Unc5b-FC can effectively inhibit retinal neovascularization induced by OIR. It may serve as a powerful and novel therapy for ischemia-induced retinal disease.

Identification of altered microRNAs in retinas of mice with oxygen-induced retinopathy

AIM: To identify disease-related miRNAs in retinas of mice with oxygen-induced retinopathy(OIR), and to explore their potential roles in retinal pathological neovascularization. METHODS: The retinal miRNA expression profile in mice with OIR and room air controls at postnatal day 17(P17) were determined through miRNA microarray analysis. Several miRNAs were significantly up-and down-regulated in retinas of mice with OIR compared to controls by quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR). Two databases including Targetscan7.1 and MirdbV5 were used to predict target genes that associated with those significantly altered mi RNAs in retinas of mice with OIR. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses were also conducted to identify possible biological functions of the target genes. RESULTS: In comparison with room air controls, 3 and 8 miRNAs were significantly up-and down-regulated, respectively, in retinas of mice with OIR. The qRT-PCR data confirmed that mmu-miR-350-3 p and mmu-miR-202-3 p were significantly up-regulated, while mmu-miR-711 and mmu-miR-30 c-1-3 p were significantly down-regulated in mice with OIR compared to controls. GO analysis demonstrated that the identified target genes were related to functions such as cellular macromolecule metabolic process. KEGG pathway analysis showed a group of pathways, such as Wnt signaling pathway, transcriptionalmisregulation in cancer, Mucin type O-glycan biosynthesis, and mitogen-activated protein kinase(MAPK) signaling pathway might be involved in pathological process of retinal neovascularization. CONCLUSION: Our findings suggest that the differentially expressed miRNAs in retinas of mice with OIR might provide potential therapeutic targets for treating retinal neovascularization.

Acetylcholinesterase inhibition ameliorates retinal neovascularization and glial activation in oxygen-induced retinopathy

AIM:To investigate whether inhibition of acetylcholinesterase(AChE)by donepezil ameliorate aberrant retinal neovascularization(RNV)and abnormal glial activation in oxygen-induced retinopathy(OIR).METHODS:A mouse model of RNV was induced in postnatal day 7(P7)mice by exposure to 75%oxygen.Donepezil was administrated to P12 mice by intraperitoneal injection.Expression and localization of AChE in mouse retinas were determined by immunofluorescence.RNV was evaluated by paraffin sectioning and hematoxylin and eosin(HE)staining.Activation of retinal M uller glial cells were examined by immunoblot of glial fibrillary acidic protein(GFAP).rMC-1.a retinal Muller cell line,was used for in vitro study.Expression of hypoxia-induced factor 1α(HIF-1α)and vascular endothelial growth factor(VEGF)were determined by Western-blot analysis,enzyme-linked immunosorbent assay(ELISA)or immunostaining.RESULTS:Aberrant RNV and glial activation was observed after OIR.Of note,retinal AChE was mainly expressed by retinal Muller glial cells and markedly increased in OIR mice.Systemic administration of donepezil significantly reduced RNV and abnormal glial activation in mice with OIR.Moreover,ischemia-induced HIF-1αaccumulation and VEGF upregulation in OIR mouse retinas and cultured rMC-1 were significantly inhibited by donepezil intervention.CONCLUSION:AchE is implicated in RNV with OIR.Inhibition of AChE by donepeizl is likely to be a potential therapeutic approach for retinal neovascular diseases.

Activated complement classical pathway in a murine model of oxygen-induced retinopathy

AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75% ±2% oxygen from postnatal 7d(P7) to P12 and then recovered in room air.For the control group, the litters were raised in room air.At the postnatal 17d(P17), gene expressions of the complement components of the classical pathway(CP),the mannose-binding lectin(MBL) pathway and the alternative pathway(AP) in the retina were determined by quantitative real-time polymerase chain reaction(RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting.· RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the periphery.The expressions of C1 qb and C4 b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B(CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H(CFH) genes were higher. The protein synthesis of the key components involved in the CP(C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1(MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not significant.CONCLUSION: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR.

Efficacy of intravitreal captopril on oxygen-induced retinopathy in mice

AIM: To study the inhibitory effect of intravitreal captopril on oxygen-induced retinopathy (OIR) in mice. METHODS: Eighty postnatal day (P)7 C57BL/63 mice were randomly divided into treated group and control group with forty mice in each group. The mice were exposed to 75% 2% oxygen for 5 days (P7-P11) and then returned to room air for 5 days (P12-P17) to induce retinal neovascularization (RNV). Beginning on P12, the mice in treated group received daily intravitreal injections of captopril(3.0mL/kg), while those in control group received daily intravitreal injections of phosphate-buffered saline (PBS) (3.0mL/kg) through P17. After anesthetized at P17, one eye was chosen randomly as experimental eye and were enucleated. RNV was examined by Adenosine diphosphate-ase (ADPase) stained retina flat-mounts and was quantitated histologically by counting the neovascular endothelial cell nuclei anterior to inner limiting membrane (ILM). The expressions of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) were measured by immunohistochemical method. RESULTS: Comparing with control group, more regular distributions, better branch and reduced density of RNV were observed in eyes of treated group. The number of neovascular cell nuclei was less in treated group than that in control group ( t =6.135, P <0.01). Stain of MMP-2 and VEGF was weaker in treated group than that in control group. CONCLUSION: The results indicate that captopril can significantly inhibit RNV in OIR mice.

Hyperbaric Oxygen Treatment for Diabetic Retinopathy and Neuropathy in a Streptozotocin Induced Diabetic Rat Model

Aim: Diabetes Mellitus is a global public health challenge with major and potentially devastating complications, and concomitant complications include retinopathy and neuropathy due to hypoxia and microvascular dysfunction. In this study, we investigated the effect of hyperbaric oxygen therapy as a method to transiently improve tissue oxygenation on diabetic retinopathy and neuropathy in a streptozotocin induced type-1 diabetic rat model (Wistar). Methods: Streptozotocin induced type-1 diabetic rats received 10 sessions of 2-h hyperbaric oxygen exposures (pO2 = 309 kPa) over 2 weeks. Animals were exposed to light stimuli to produce light evoked potentials to estimate the effect of oxygen treatment on diabetic retinopathy. Sciatic nerves were exposed and stimulated to produce muscle evoked potential, which were recorded in the muscles of the foot and subsequently used to evaluate the effect of oxygen treatment on diabetic neuropathy. Results: We found significantly shorter light evoked potential latency and increased amplitude in hyperbaric oxygen treated animals. No change was found in nerve conduction. Conclusions: This study showed that hyperbaric oxygen therapy is a potentially effective treatment for diabetic retinopathy, improving both latency and amplitude of light evoked potentials.

AB017.Investigation of the effect of lymphocyte-derived microparticles on retinal macrophages in the oxygen-induced retinopathy model

Background:Retinopathy of prematurity(ROP)is the major cause of blindness in children,mainly caused by the retinal neovascularization(NV).Mounting of evidences shown that macrophage plays a pivotal role in the regulation of angiogenesis in ROP.Numerous studies confirmed that the deletion of macrophage significantly reduce the neovascularized areas in the oxygen-induced retinopathy(OIR)model.We have been studied the effect of lymphocyte derived-microparticles(LMPs)over ten years.LMPs are extracellular vesicles derived from apoptotic human CEM T lymphocytes.Our previous studies demonstrated that LMPs possess strong anti-angiogenic effect.Recently we observed that LMPs are capable to switch the phenotype of macrophage,thus to suppress the choroidal neovascularization(CNV).However,the role of LMPs on macrophage in ROP has not been clarified.Thus,my project is to disclose the relationship between LMPs and macrophage in ROP using the OIR model.Hypothesis:LMPs may inhibit retinal NV in the OIR model through targeting at macrophage by affecting the migration of macrophage,thus to inhibit pathological angiogenesis in ROP.Methods:Cell culture[RAW 264.7 and bone marrow-derived macrophage(BMDM)]for cell migration and viability assay.Generate the OIR model for in vivo detection of macrophage recruitment.Quantification of retinal NV,immunohistostaining of the macrophage in vivo,ex vivo retinal explants for cell migration and qPCR.Results:LMPs do not affect RAW 264.7 and BMDM cell viability(P>0.05).LMPs significantly decrease the BMDM cell migration indirectly(P<0.05).I successfully generate the OIR model and confirm that more macrophages infiltrate during retinal angiogenesis with counting the F4/80 immunostaining in the retinal flat mount.LMPs exert inhibiting effect on retinal angiogenesis through decreasing the migration of macrophages in vivo.Conclusions:LMPs have the negative effect on retinal angiogenesis via reducing the infiltrated macrophages to the neovascularized areas in the OIR model.

The progress of prophylactic treatment in retinopathy of prematurity

Retinopathy of prematurity（ROP） is a retinal vascular disorder frequently found in premature infants.Different therapeutic strategies have been developed to treat ROP.However,there are still many children with ROP suffering by severe limitations in vision or even blindness.Recently,ROP has been suggested to be caused by abnormal development of the retinal vasculature,but not simply resulted by retinal neovascularization which takes about 4 to 6 wk after birth in premature infants.Thus,instead of focusing on how to reduce retinal neovascularization,understanding the pathological changes and mechanisms that occur prior to retinal neovascularization is meaningful,which may lead to identify novel target（s） for the development of novel strategy to promote the healthy growth of retinal blood vessels rather than passively waiting for the appearance of retinal neovascularization and removing it by force.In this review,we discussed recent studies about,1） the pathogenesis prior to retinal neovascularization in oxygen-induced retinopathy（OIR;a ROP in animal model） and in premature infants with ROP;2） the preclinical and clinical research on preventive treatment of early OIR and ROP.We will not only highlight the importance of the mechanisms and signalling pathways in regulating early stage of ROP but also will provide guidance for actively exploring novel mechanisms and discovering novel treatments for early phase OIR and ROP prior to retinal neovascularization in the future.

Expression and function of Delta-like ligand 4 in a rat model of retinopathy of prematurity

The Delta-like ligand 4/Notch signaling pathway was shown to participate in the process of retinal development and angiogenesis. However, the function of the Delta-like ligand 4/Notch signaling pathway in retinopathy of prematurity requires further study. Retinopathy of prematurity was induced in 5-day-old Sprague-Dawley rats exposed to hyperoxia for 7 days, and then returned to room air. Reverse transcription-PCR and western blot revealed that Delta-like ligand 4 levels decreased at postnatal day 12 and increased at postnatal day 17 in retinopathy of prematurity rats. Flat-mounted adenosine diphosphatase stained retina and hematoxylin-eosin stained retinal tissue slices showed that the clock hour scores and the nuclei counts in retinopathy of prematurity rats were significantly different compared to normal control rats. After retinopathy of prematurity rats were intravitreally injected with Delta-like ligand 4 monoclonal antibody to inhibit the Delta-like ligand 4/Notch signaling pathway, there was a significant increase in the severity of retinal neovascularization （clock hours） in the intravitreally injected eyes. The nuclei count was highly correlated with the clock hour score. These results suggest that Delta-like ligand 4/Notch signaling plays an essential role in the process of physiological and pathological angiogenesis in the retina.

Maternally expressed gene 3 regulates retinal neovascularization in retinopathy of prematurity

The mouse model of oxygen induced retinopathy is suitable for the study of various retinal neovascularization diseases,including retinopathy of prematurity.The maternally expressed gene 3(MEG3)has been demonstrated to have an inhibitory effect on diabetic retinopathy.In this study,we investigated the role of MEG3 overexpression in oxygen-induced retinopathy in mice.The results showed that MEG3 overexpression effectively inhibited the production of retinal neovascularization in oxygen-induced retinopathy mice.It acts by down-regulating the expression of phosphoinositide 3-kinase,serine/threonine kinase,and vascular endothelial growth factor and pro-inflammatory factors.MEG3 overexpression lentivirus has a future as a new method for the clinical treatment of retinopathy of prematurity.The animal experiments were approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University,China(approval No.2016PS074K)on February 25,2016.

Experimental models of retinopathy of prematurity

Background:Retinopathy of prematurity(ROP)is considered as the most common reason for blindness in children,particularly in preterm infants.The disease is characterized by the dysregulation of angiogenic mechanisms due to preterm birth,leading ultimately to vascular abnormalities and pathological neovascularization(NV).Retinal detachment and vision loss could represent a concrete risk connected to the most severe forms of ROP,also characterized by inflammation and retinal cell death.Methods:During the last decades,many animal models of oxygen-induced retinopathy(OIR)have been recognized as useful tools to study the mechanisms of disease,since they reproduce the hallmarks typical of human ROP.Indeed,modulation of retinal vascular development by exposure to different oxygen protocols is possible in these animals,reproducing the main pathological phenotypes of the disease.The easy quantification of abnormal NV and the possibility to perform electrophysiologic,histological and molecular analyses on these models,make OIR animals a fundamental instrument in studying the pathophysiology of ROP and the effects of novel treatments against the disease.Discussion:Here,the most commonly used OIR protocols in rodents,such as mice and rats,are described as well as the main pathological outcomes typical of these models.Despite their limitations and variables which should be considered whilst using these models,OIR models display several characteristics which have also been confirmed in human patients,validating the usefulness of such animals in the pre-clinical research of ROP.

Long-lasting impairments in rodent oxygen-induced retinopathy measured by retinal vessel density and visual function

In mild or moderate retinopathy of prematurity(ROP), retinal vessels undergo obliteration, proliferation, and regression. Despite complete regression of vessel abnormalities, a variety of visual impairments have been reported. Rodent oxygen-induced retinopathy(OIR) is widely used as a model to study ROP. However, the long-term changes of OIR model remain unclear. The aim of this study is to examine long term changes of retinal vessel and visual function in a rodent OIR model resembling human mild or moderate ROP. In this study, after subjecting the animals to 80% oxygen(O_2) for 5–7 d, the retinal vessel density at postnatal day 12(P12) was approximately 30% lower than that in the age-matched control, but this difference was not significant between the groups. Vessel abnormalities, such as vessel tortuosity, neovascular tufts, and the number of vessels protruding into the vitreous, peaked between P17 and P20. Despite the regression of many abnormalities, vessel density in the OIR group was 36% and 32% lower than that in the control animals at 6 weeks and 4 months, respectively. The visual acuity and contrast sensitivity were impaired in the OIR group when measured at 2, 3 and 4 months. Therefore, the rodent OIR model exhibited long-lasting reduction in retinal vessel density and visual impairments, similar to those observed in mild or moderate human ROP. This study suggests that the rodent OIR model can be used to explore possible interventions for mild and moderate human ROP.

治疗剂量高压氧对胎鼠及新生鼠视网膜血管的影响

目的：探讨临床治疗剂量高压氧（HBO）对胎鼠及新生鼠视网膜的影响.方法：SD新生大鼠,随机分为实验1～3组、对照组（常压空气组）及ROP模型组各5只,实验1组于孕鼠分娩前单纯予治疗剂量的HBO 5 d（2ATA,800mL/L O2,1h）、实验2组新生大鼠不仅予宫内HBO,且出生后7d起继续HBO 5 d、实验3组仅予新生鼠7 d HBO（2ATA,800mL/L O2,1h）连续5d;对照组置于常压空气中;ROP模型组第7d常压吸氧（800mL/L）5d,然后吸空气.全部新生大鼠于17d制作视网膜组织切片,计数突破视网膜内界膜的细胞核数目及免疫组织化学方法测定血管内皮生长因子（VEGF）在视网膜的表达.结果：实验1～3组突破视网膜内界膜的细胞核数目与对照组相比,差异无统计学意义（P〉0.05）,ROP模型组与对照组及实验1～3组相比,差异有统计学意义（37.9±6.1 vs 1.4±0.9,1.6±1.1,1.4±0.8,P〈0.01）.实验各组及对照组的VEGF的表达均以弱阳性为主,均弱于ROP模型组,差异有统计学意义（P〈0.01）.结论：临床治疗剂量高压氧对胎鼠及新生鼠视网膜无影响.

氧诱导小鼠视网膜新生血管发生中乙酰肝素酶及串珠素的表达

目的研究小鼠视网膜新生血管发生过程中乙酰肝素酶(HPA)及其作用底物串珠素在视网膜中的表达。方法将65只新生幼鼠于生后7d在体积分数(75±2)%高氧环境中饲养5d后,再置于相对低氧环境中诱导产生视网膜新生血管为高氧诱导组。另外65只新生幼鼠在正常环境中饲养作为正常对照组。分别在小鼠生后第12、13、17、21、30天通过荧光素眼底血管造影(FFA)和视网膜病理切片观察视网膜新生血管的形态变化。通过逆转录聚合酶链反应(RT-PCR)分别检测不同时间点视网膜组织中HPA和串珠素在mRNA水平的变化,Western blot检测不同时间点视网膜组织中HPA在蛋白水平的表达变化。结果高氧诱导组与正常对照组的HPA mRNA表达水平差异有统计学意义(Fgroup=16.303,P=0.000),各时间点的HPAmRNA表达水平差异有统计学意义(Ftime=18.614,P=0.000),生后第12、13、17、21天相应时间点2组小鼠视网膜HPAmRNA的表达水平差异均有统计学意义(P=0.001,P=0.000,P=0.000,P=0.001)。高氧诱导组与正常对照组HPA蛋白表达水平差异有统计学意义(Fgroup=458.134,P=0.000),各时间点的HPA蛋白表达水平差异有统计学意义(Ftime=78.466,P=0.000)。高氧诱导组与正常对照组的串珠素mRNA表达水平差异有统计学意义(Fgroup=7.351,P=0.013),各时间点的串珠素mRNA表达水平差异有统计学意义(Ftime=9.098,P=0.000)。生后第13、17、21天的高氧诱导组小鼠视网膜串珠素mRNA的表达水平与正常对照组相应时间点,差异均有统计学意义(P=0.048,P=0.000,P=0.003)。伴随着视网膜新生血管的增多和消退,HPA在基因和蛋白水平及串珠素在基因水平的表达均呈先升高后降低的趋势。结论HPA及其作用底物可能是促进视网膜新生血管生长的重要因素。

高压氧对糖尿病视网膜病变的影响

目的观察高压氧对糖尿病视网膜病变的疗效。方法 82例糖尿病视网膜病变患者随机分为观察组和对照组各41例,两组均给予羟苯磺酸钙胶囊口服及糖尿病综合治疗,在此基础上,观察组辅予高压氧治疗,并检测治疗前后两组患者眼底的变化和血液流变学指标变化。结果观察组显效21例,有效16例,无效4例,总有效率90.24%;对照组显效15例,有效13例,无效13例,总有效率68.29%,两者比较差异有统计学意义(P<0.05)。治疗后两组血液流变学指标均下降,观察组下降更显著,改善更理想,两组比较差异有统计学意义(P<0.01)。结论高压氧可显著改善糖尿病患者的血液流变学异常,改善患者视网膜缺血、低氧状态,对糖尿病视网膜病变有较好的疗效。

高压氧结合激光光凝治疗糖尿病性黄斑水肿

目的了解高压氧对糖尿病性黄斑水肿的疗效。方法糖尿病性黄斑水肿病人34例61眼,病例随机等分为高压氧加光凝组和光凝组。两组黄斑水肿程度基本齐同。光凝组在黄斑区行局灶或格栅样激光光凝,高压氧加光凝组在光凝基础上加高压氧(0.22 MPa)治疗,每日60分钟,疗程12天。结果治疗前对数视力:高压氧加光凝组为(4.3±0.5),光凝组为(4.1±0.7);治疗3个月后视力提高:高压氧加光凝组15眼(15/31)多于光凝组9眼(9/30)。高压氧加光凝组对数视力(4.5±0.5)较治疗前提高(t=3.042,P=0.005);光凝组(4.1±0.7)与治疗前比较,差异无统计学意义(t=1.394,P=0.174)。眼底血管荧光造影或光学相干断层扫描显示,高压氧加光凝组黄斑水肿消退有效率较光凝组高(77.4%比46.7%,2χ=6.139,P=0.013)。治疗后黄斑水肿消退分级与治疗视力改善、高压氧治疗、黄斑水肿程度、空腹血糖、总胆固醇、舒张压、糖化血红蛋白及糖尿病病情相关,而与糖尿病视网膜病变分期和病程、治疗前视力、是否用胰岛素、收缩压、甘油三酯、血尿素氮和血肌酐无关。结论高压氧联合黄斑区格栅样激光光凝有助于糖尿病性黄斑水肿吸收及部分病人视力改善。

高压氧治疗脑损伤合并视网膜病变婴幼儿的眼底随访观察

目的探索高压氧治疗脑损伤合并视网膜病变婴幼儿的眼底变化。方法54例脑损伤合并视网膜病变婴幼儿,均进行高压氧疗法治疗。分析高压氧治疗前、中、后眼底筛查结果和高压氧治疗后电话随访结果。结果高压氧治疗前眼底筛查:单侧早产儿视网膜病变(ROP)3例,双侧ROP 17例,视网膜冷凝术后11例;高压氧治疗中和治疗后眼底筛查(10、20、30次各复查1次):正常10例,稳定12例,好转4例,黄斑病变3例,右眼视网膜出血1例,死亡1例。2019年12月电话随访结果:28例眼科检查正常,2例黄斑病变患儿(双胞,男,5岁7月龄)家长自诉正常(拒绝眼科复查),另1例黄斑病变患儿失联,无新的视网膜病变诱发病例。结论脑损伤合并视网膜病变婴幼儿采用高压氧治疗前后未发现加重视网膜病变,也未见诱发视网膜病变新病例,鉴于样本量不大,有待于扩大研究进一步验证其高压氧治疗的安全性。

高压氧联合胰激肽原酶对老年糖尿病伴视网膜病变患者的相关性影响

目的探讨高压氧联合胰激肽原酶对老年糖尿病伴视网膜病变(DR)患者视网膜血流、血管内皮生长因子(VEGF)的影响。方法选取我院收治的老年DR患者146例,按随机数字表法分为对照组和研究组,每组各73例(146眼),对照组予以安慰剂治疗,研究组予以高压氧联合胰激肽原酶治疗,比较两组间视网膜血流动力学指标、血清VEGF、胰岛素样生长因子(IGF-1)、碱性成纤维细胞生长因子(bFGF)水平、血清炎性细胞因子水平、临床疗效及不良反应发生率。结果对照组有效率低于研究组,差异有统计学意义(P<0.05);与对照组比较,研究组治疗后视网膜中央动脉VPS、VED水平较高,RI水平较低,治疗后血清VEGF、IGF-1、bFGF水平较低,治疗后血清超敏C反应蛋白(hs-CRP)、白细胞介素(IL-6)水平较低,差异有统计学意义(P<0.05);治疗中出现的不良反应为胃部不适、头晕、耳鸣、倦怠,两组不良反应发生率差异无统计学意义(P>0.05)。结论高压氧联合胰激肽原酶能有效改善老年DR患者视网膜血流动力学指标,降低血清VEGF、IGF-1、bFGF及炎性细胞因子水平,抑制血管增殖和炎症反应,临床疗效和安全性较好。

microRNA-218 Inhibits Oxygen-induced Retinal Neovascularization via Reducing the Expression of Roundabout I

Background： The mechanisms of pathological retinal neovascularization （RNV） remain unknown. Several microRNAs were reported to be involved in the process of RNV. Oxygen-induced retinopathy （O1R） is a useful model to investigate RNV. Our present work explored the expression and the role of microRNA-128 （miR-218） in oxygen-induced RNV. Methods： OIR was used to establish RNV model. The expression level ofmiR-218 in the retina from OIR mice was assessed by quantitative real-time reverse transcriptase polymerase chain reaction. Fluorescein angiography was performed in retinae of OIR mice, and RNV was quantified by hematoxylin and eosin staining to evaluate the effect of pCDH-CMV-miR-218 intravitreal injection on RNV in OIR mice. Roundabout 1 （Robol） expression was detected by Western blotting in mouse retinal vascular endothelial cells expressing a high or low level of miR-218 and retinal tissues from OIR mice. Cell migration was evaluated by scratch wound assay. Results： In OIR mice, the expression level of miR-218 was significantly down-regulated （P = 0.006）. Retinal Robol expression was significantly increased at both mRNA and protein levels （P = 0.001, 0.008： respectively）, miR-218 intravitreal injection inhibited retinal angiogenesis in OIR mice, and the restoration of miR-218 in retina led to down-regulation of Robol. Conelusions： Our experiments showed that restoration ofmiR-218 inhibited retinal angiogenesis via targeting Robo 1. MiR-218 contributed to the inhibition of retinal angiogenesis and miR-218 might be a new therapeutic target for preventing RNV.