中药散血明目片抑制兔视网膜静脉阻塞后视网膜VEGF和bFGF的表达

目的:探讨活血通脉利水明目作用的中药散血明目片防治视网膜静脉阻塞(retinal vein occlusion,RVO)并发新生血管的作用。方法:将家兔48只96眼随机分为4组,每组12只24眼。A健康空白组;B模型组;C血栓通组;D散血明目片组。采用激光光凝法建立兔RVO模型,分别于术后3,7,14,21d用空气栓塞法处死动物,即刻摘取眼球石蜡包埋切片。免疫组化法观察兔视网膜组织中血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)的表达。结果:成功建立了RVO模型。D组与B组比较,视网膜组织中VEGF含量(21d时分别为0.442±0.034和0.583±0.056)和bFGF含量(21d时分别为0.419±0.040和0.514±0.056)明显减少,差异有统计学意义(P<0.05),与C组比较差异无统计学意义。结论:活血通脉利水明目之散血明目片能抑制视网膜面VEGF和bFGF的高表达。     

Alterations in protein tyrosine kinase pathways following retinal vein occlusion in the rat.

PURPOSE: To determine whether an experimental retinal vein occlusion in the rat activates protein tyrosine kinase pathways and increases angiogenic growth factors in the retina. METHODS: Retinal vein occlusion (RVO) was induced in the rat retina with argon laser photocoagulation. Retinas were collected at 2 days, 1, 2, and 4 weeks after RVO and divided into halves: one half represented an area within the distribution of the occluded vein [RVO(IN)] and the other half represented an area outside the distribution of the occluded vein [RVO(OUT)]. RVO(IN) and (OUT) were examined by western blot analysis of tyrosine-phosphorylated proteins, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and 3 signal proteins in the tyrosine kinase pathways: phospholipase Cgamma (PLCgamma), phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK). RESULTS: RVO caused a severe capillary nonperfusion in RVO(IN). Overall tyrosine-phosphorylated proteins were increased after RVO, especially in RVO(IN) at 2 days and 1 week. VEGF and bFGF were markedly increased in RVO(IN) at 2 days and 1 week. Tyrosine-phosphorylated PLCgamma, PI3K, and MAPK were also increased in RVO(IN) at these time points. CONCLUSIONS: RVO caused an increase in overall protein tyrosine phosphorylation in the rat retina. This increase was associated with an increase in angiogenic growth factors (VEGF and bFGF). These results suggest that protein tyrosine kinase pathways are activated during retinal ischemia and may play a role in mitogenesis of vascular endothelial cells and other responses in the retina after RVO.     

经瞳孔温热疗法照射对视网膜组织中VEGF和MMP-1 mRNA表达的影响

目的研究经瞳孔温热疗法（transpupillary thermotherapy,TTT）照射对视网膜组织中血管内皮生长因子（vascular endothelial growth factor，VEGF）和基质金属蛋白酶-1（matrix metalloproteinase-1，MMP—1）表达的影响。方法使用唧照射正常灰免视网膜．激光参数为：3min光斑直径，1min曝光时间，450mW功率。每眼照射15点。于照射后1d、3d、7d、2周和3周处死动物并取视网膜组织。抽提RNA后使用RT-PCR方法进行扩增。结果与正常视网膜相比，TTT照射后1d和3d时VEGF mRNA表达降低，7d时恢复正常；MMP-1 mRNA在TTT照射后升高，持续至2周，3周时明显下降。结论TTT照射可能通过降低视网膜组织VEGF的表达来起到抑制新生血管的作用．TTT照射引起MMP-1的表达升高可能通过增加胶原成分的降解来促进新生血管纤维膜的回退。     

Natural course of experimental retinal vein occlusion in rabbit; arterial occlusion following venous photothrombosis

BACKGROUND: Retinal vein occlusion (RVO) is the second leading cause of vascular eye disease. Currently there is no definite treatment for this condition. Animal models could be potentially helpful in developing new treatments; however, it is essential to understand the differences these models may have with human RVO. The aim of our study was to examine the course of experimentally created retinal vein occlusion (RVO) in rabbits. METHODS: Twenty-nine pigmented rabbits were included in the study. RVO was created in all using an argon green laser following intravenous injection of Rose Bengal. A laser was applied to all major veins at the optic disc margin to mimic central retinal vein occlusion. Animals were followed-up for a maximum of 2 months. RESULTS: Immediately following laser application, blood flow ceased or the flow was extremely slow in the retinal veins in all cases. At day 2 post laser, 86% showed significant retinal hemorrhages. On FA, no retinal blood flow was observed in the eye (neither arteries nor veins) in the majority of rabbits. Between weeks 1 and 3, laser sites reopened and partial or complete revascularization of both retinal arteries and veins occurred; however, the vascular pattern was abnormal. CONCLUSIONS: RVO in rabbits has a different course than in human and it can be classified into three stages. At stage 1 (the first few days after laser photothrombosis), there is a retrograde propagation of the blood clot in the retinal veins that extends to the retinal arteries and choriocapillaries. As a result, there is no retinal blood flow at this stage in most cases. At stage 2 (between weeks 1 and 3), partial or complete revascularization occurs but the vessels have an abnormal pattern. At stage 3 (after week 3) no significant change takes place.     

视网膜静脉阻塞患者血浆和泪液中血管内皮生长因子表达的研究

目的　观察视网膜静脉阻塞（ｒｅｔｉｎａｌｖｅｉｎｏｃｃｌｕｓｉｏｎ,ＲＶＯ）患者血浆和泪液中血管内皮生长因子（ｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｇｒｏｗｔｈｆａｃｔｏｒ,ＶＥＧＦ）的表达情况。方法　选取我院确诊的２８例ＲＶＯ患者,收集血浆和泪液样本,通过酶联免疫吸附试验测定ＶＥＧＦ表达水平,在１ｄ、２周和４周使用光学相干断层扫描检查中央视网膜厚度（ｃｅｎｔｒａｌｒｅｔｉｎａｌｔｈｉｃｋｎｅｓｓ,ＣＲＴ）,另选健康志愿者３０人作为对照组,比较两组血浆和泪液中ＶＥＧＦ、ＣＲＴ表达差异。结果　各时间点,ＲＶＯ组血浆中ＶＥＧＦ表达水平显著高于对照组（均为Ｐ＜０．０５）,１ｄＲＶＯ组泪液ＶＥＧＦ表达水平与对照组差异无统计学意义（Ｐ＞０．０５）。ＲＶＯ组血浆和泪液中ＶＥＧＦ表达水平呈微弱正相关（Ｐ＜０．０５）,而对照组中这种相关性稍强（Ｐ＜０．０５）。两组２周后ＣＲＴ明显增加,１ｄ与２周ＣＲＴ值差异均有统计学意义（均为Ｐ＜０．０５）,２周与４周差异均无统计学意义（均为Ｐ＞０．０５）,各时间段ＲＶＯ组与对照组差异有统计学意义（Ｐ＜０．０５）。结论　ＲＶＯ患者泪液中ＶＥＧＦ表达水平及ＣＲＴ与健康人比较显著升高,血浆与泪液中ＶＥＧＦ表达水平的变化有一致性,泪液检测作为非侵入性的检测方式,对ＲＶＯ的早期诊断有较高的临床应用价值。     

血管内皮生长因子在新生小鼠视网膜的表达

目的 研究血管内皮生长因子（vascular endothelial growth factor,VEGF)与新生小鼠视网膜血管系统形成的内在联系，方法 分别于小鼠出生后3d,1、2、4周以免疫组化观察VEGF在视网膜的表达，并与视网膜铺片和光镜结果相对照。结果 小鼠出生后视网膜血管系统由视盘处呈放射状穿出，逐渐由后极部向周边部，视网膜病理切片显示；出生后3d时，视网膜只有2层，即神经节细胞层和神经母细胞层，内层毛细血管仅限于视网膜后极及中周部，7d时外丛状层形成，出生后14d，视网膜外层毛细血管发育基本完成，出生后28d，视网膜与14d时大致相似，VEGF免疫组化结果显示；出生后3d，阳性信号位于神经节细胞层和神经母细胞层内，外缘，7d时，VEGF明显表达在神经节细胞层，外丛状层和几乎全层内核层，出生后14d及28d。当视网膜血管系统发育基本完成时，VEGF阳性细胞数量和强度都明显减少和减弱。结论 本研究提示，VEGF的表达在空间和时间上与视网膜血管形成密切相关，VEGF的存在对于小鼠视网膜血管系统的形成及维持正常生理功能可能至关重要。     

Effect of anti-VEGF treatment on nonperfusion areas in ischemic retinopathy

In recent years, retinal ischemia such as that which occurs in diabetic retinopathy (DR) and retinal vein occlusion (RVO) has become a hotspot of ischemic retinopathy research. High levels of vascular endothelial growth factor (VEGF) are recognized as a major cause of macular edema (ME) in DR and RVO. High concentrations of VEGF in the vitreous can lead to serious retinal ischemia and hypoxia and form retinal nonperfusion areas (NPAs). Different levels of retinal ischemia can represent disease severity and progression. Anti-VEGF therapy as the first-line treatment for ME has been found to be effective in improving vision, but there are still disputes about whether anti-VEGF therapy could improve retinal ischemia and achieve reperfusion of previously developed retinal NPAs. Here, we review and summarize studies of the effects of anti-VEGF drugs on retinal ischemia, especially NPAs.     

Vascular endothelial growth factor is elevated in ocular fluids of eyes harbouring uveal melanoma: identification of a potential therapeutic window

BACKGROUND: Improved local treatment of uveal melanoma makes it possible for many patients to retain the affected eye, but a proportion will develop secondary complications such as neovascularisation of the iris (NVI) and require enucleation. Although vascular endothelial growth factor A (VEGF-A) is known to correlate with NVI and can cause NVI in experimental models, this pro-angiogenic cytokine is consistently reported to be absent in uveal melanoma. Novel anti-VEGF therapies are now in clinical trial, and the authors therefore wished to determine whether VEGF-A was indeed elevated in melanoma bearing eyes. METHODS: VEGF-A concentrations were measured in aqueous and vitreous from 19 and 30 enucleated eyes respectively. RESULTS: Elevated VEGF-A concentrations (up to 21.6 ng/ml) were found in melanoma bearing eyes compared with samples from patients undergoing routine cataract extraction (all had values below 0.96 ng/ml). Immunohistochemistry showed VEGF-A protein in the iris and/or ciliary body of 54% and basic fibroblast growth factor (bFGF) in 82% of the eyes examined. VEGF was found to a limited extent and at very low levels in only 9% of these tumours. Aqueous or vitreous VEGF levels showed no apparent correlation with retinal detachment, tumour size, vascularity, or immunohistochemistry. Though limited in number, the highest VEGF levels correlated with previous radiation therapy, and with the presence neovascularisation of the iris or optic nerve head. bFGF was not significantly elevated in ocular fluids: it is known to be a pro-angiogenic agent and was detected in the majority of primary uveal melanomas. CONCLUSION: Based on this study, though the source of VEGF within eyes harbouring uveal melanoma is not clear, these data suggest that anti-VEGF therapy might prove useful in the management of some patients with NVI secondary to uveal melanoma.     

血管内皮生长因子及其受体在实验性脉络膜新生血管中的表达

目的 探讨血管内皮生长因子(VEGF)及其FLK1受体在氪激光诱导的棕色挪威(BN)大鼠脉络膜新生血管(CNV)中的表达。方法 应用氪激光对30只雄性BN大鼠实验眼进行视网膜光凝,创建CNV模型,分别于光凝后3、7、14、21、28及56 d行荧光素眼底血管造影(FFA),处死大鼠后摘除眼球,制作组织病理学标本观察,原位杂交检测VEGFmRNA,免疫组化检测VEGF和FLK1受体。结果 正常BN大鼠视网膜神经节细胞层、内核层、色素上皮层、视网膜及脉络膜血管内皮细胞中均表达VEGFmRNA。实验眼光凝后3 d,光凝区视网膜神经节细胞层、内核层、外核层缺损区、视网膜及脉络膜血管内皮细胞均表达VEGFmRNA,此时视网膜下未形成CNV;3-21 d视网膜内VEGFmRNA表达水平逐渐下降(P<0.01);21 d与28 d和56 d比较,VEGFmRNA表达水平差异无显著意义(P>0.05)。光凝后7 d,FFA检查可见光凝区有圆盘状荧光素渗漏。病理切片可见视网膜下形成CNV,CNV中VEGFmRNA表达阳性;7～21 d,CNV中VEGFmRNA阳性染色面积及吸光度(A)值逐渐增加(P<0.01);21 d后VEGFmRNA表达水平差异无显著意义(P>0.05)。正常视网膜和脉络膜血管内皮细胞及视网膜神经节细胞层FLK1受体表达阳性;光凝后7 d,CNV中FLK1受体表达阳性;随CNV的增生,FLK1受体阳性染色面积及A值逐渐增加(P<0.01);21 d与28 d和5     

抗血管内皮生长因子药物治疗对视网膜静脉阻塞黄斑水肿患者视网膜毛细血管影响的研究现状

玻璃体腔注射抗VEGF药物是目前治疗视网膜静脉阻塞(RVO)黄斑水肿的主要手段,其能明显抑制新生血管,减轻水肿,提高患者视力。但VEGF是血管内皮细胞的存活因子,其是否会导致视网膜缺血进展以及是否对视网膜毛细血管产生影响值得临床关注。就目前来看,大多学者认为,从拱环形态改变以及浅层、深层视网膜毛细血管层量化黄斑中心凹无血管区面积、视网膜无灌注区大小及黄斑区视网膜血流密度等方面观察,抗VEGF药物治疗RVO黄斑水肿并不会加重视网膜毛细血管的闭塞。并且,这些指标的变化可能与患者需要治疗的次数、视力预后等有一定的关系。今后随着OCT血管成像的逐渐普及以及抗VEGF药物治疗次数和时间的延长,期待更大样本、更长随访时间的研究深入分析抗VEGF药物治疗对RVO黄斑水肿患者视网膜毛细血管的确切影响。     

Differences in the temporal expression of regulatory growth factors during choroidal neovascular development

Although the roles of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) in pathologic neovascularization have been well characterized in certain tissues, their particular functions and expression patterns in choroidal neovascularization (CNV) have not been clearly established. After localized laser trauma to Bruch's membrane to induce CNV development, the temporal changes in mRNA and protein expression of these 3 cytokines were documented and compared histologically to areas of immunofluorescence, the proliferation of endothelial cells, neovascular development, and temporal changes in vascular permeability. Changes in mRNA and protein levels of bFGF and HGF occurred quickly and reached peak expression within hours. This activity corresponded in time to intense and localized immunofluorescence for these cytokines within the choriocapillaris within laser lesion sites. During this same initial time period, mRNA upregulation of VEGF occurred, primarily within the neural retina and this expression corresponded to intense immunolabeling of Müller cells immediately adjacent to the lesion sites. By 3 days after lasering, increased VEGF₁₆₄ protein expression was measurable, whereas early neovascular development histologically corresponded to HGF and bFGF mRNA expansion into the developing choroidal neovascular membrane (CNVM). At 7 days, CNV expansion, maturation, and increased vascular permeability corresponded to peak VEGF mRNA and protein expression and to immunofluorescence of the CNVM. Differences also occurred in the expression of precursor and activated isoforms of these cytokines in the retinal pigment epithelium/choroid as compared to those in the retina. These molecular and immunocytochemical results suggest that bFGF and HGF may be important as initial regulators neovascularization in this CNV model; whereas VEGF may be important during later phases of angiogenesis and neovascular hyperpermeability.     

血管生成抑制因子k4k5对实验性脉络膜新生血管的抑制作用

目的 评价血管生成抑制因子kringle4-5能否抑制氩激光诱导小鼠的脉络膜新生血管。 方法 通过氩 激光眼底光凝诱导C57BL/6J小鼠产生脉络膜新生血管，随机分为对照组、低剂量组和高剂量组，每组各16只小鼠。在眼底氩激光光凝后立即对3组小鼠分别球后注射林格氏液、kringle4-5 20、50 μg。在光凝后7、14 d通过荧光素眼底血管造影(fundus fluorescence angiography,FFA)评价脉络膜新生血管的发生率。光凝后14 d将动物处死，行组织学检查及观察CD105的表达。用免疫组织化学方法检测光凝后14 d各组血管内皮生长因子(vascular endothelial growth factor, VEGF)及碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)的表达。 结果 对照组，光凝后14 d脉络膜新生血管的发生率为64.3%，低剂量组和高剂量组脉络膜新生血管的发生率分别为51.2%（P＜0.05）、44.1%（P＜0.01）。组织学检查显示治疗组脉络膜新生血管(choroidal neovascularization,CNV)范围小于对照组，与剂量呈正相关，高剂量组差异有显著性的意义(P＜0.05) ,而且CD105的表达，治疗组少于对照组(P＜0.05)。VEGF及bFGF的表达在对照组与治疗组之间差异无显著性的意义。 结论 Kringle4-5对激光诱导小鼠的实验性CNV具有抑制作用，在此剂量范围，对VEGF及bFGF的表达无明显影响。（中华眼底病杂志，2003，19：201-268）     

Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases

The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age‐related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis‐dependent pathologies in the eye and non‐ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen‐induced retinopathy, laser‐induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF‐specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research.     

血管内皮生长因子 A的选择性剪接与眼内新生血管的生成

眼内新生血管的生成是多种眼病致盲的重要原因.血管内皮生长因子A(VEGF-A)家族是促进眼内新生血管生成的关键因素,其通过调控病理性血管的发生和增加血管的通透性而起作用.VEGF-A依选择性剪接方式的不同,可形成2个蛋白家族,分别是具有促血管生成作用的VEGFxxx家族和具有抗血管生成作用的VEGFxxxb家族.VEGFxxxb家族蛋白在正常眼组织中均有表达,而在糖尿病性视网膜病变患者的眼组织中表达水平降低.VEGF165b是VEGFxxxb家族中最早分离出来且研究最为广泛的分子结构,其可以明显抑制视网膜前新生血管的生成,而对视网膜生理性血管的发生无抑制作用.随着对VEGFxxxb家族研究的逐步深入,选择性剪接调节VEGFxxx与VEGFxxxb两者之间的平衡,可作为糖尿病性视网膜病变、年龄相关性黄斑变性等眼内新生血管性疾病的治疗新策略.     

青蒿琥酯对大鼠实验性视网膜分支静脉阻塞的抑制作用

目的 探讨青蒿琥酯(Art)对大鼠实验性视网膜分支静脉阻塞(BRVO)的抑制作用。方法 取SPF级雌性Wistar大鼠150只,将动物随机分为6组,每组25只,右眼为实验眼：空白对照组、模型对照组(玻璃体内注射生理盐水)、康柏西普组、Art高浓度(50.0 mg·L^-1)组、Art中浓度(25.0 mg·L^-1)组、Art低浓度(12.5 mg·L^-1)组;空白对照组采用未造模大鼠进行实验,其他各组采用BRVO模型大鼠进行实验。采用光化学法建立大鼠BRVO模型。模型建立后行玻璃体内注射给药,注药后1 d、3 d、7 d及14 d行眼底照相观察血管阻塞、视网膜水肿情况;行HE染色观察视网膜组织形态,并测量视网膜内层厚度;实时荧光定量PCR检测视网膜组织VEGF、HIF-1αmRNA表达情况。结果 玻璃体内注药后1 d,模型对照组,康柏西普组,Art高、中、低浓度组大鼠出现视网膜静脉阻塞、迂曲扩张及视网膜出血水肿表现。玻璃体内注药后7 d,康柏西普组和Art高、中、低浓度组大鼠视网膜静脉再通,仅有小部分静脉血管阻塞;而康柏西...     

血管内皮生长因子 A的选择性剪接与眼内新生血管的生成

眼内新生血管的生成是多种眼病致盲的重要原因.血管内皮生长因子A(VEGF-A)家族是促进眼内新生血管生成的关键因素,其通过调控病理性血管的发生和增加血管的通透性而起作用.VEGF-A依选择性剪接方式的不同,可形成2个蛋白家族,分别是具有促血管生成作用的VEGFxxx家族和具有抗血管生成作用的VEGFxxxb家族.VEGFxxxb家族蛋白在正常眼组织中均有表达,而在糖尿病性视网膜病变患者的眼组织中表达水平降低.VEGF165b是VEGFxxxb家族中最早分离出来且研究最为广泛的分子结构,其可以明显抑制视网膜前新生血管的生成,而对视网膜生理性血管的发生无抑制作用.随着对VEGFxxxb家族研究的逐步深入,选择性剪接调节VEGFxxx与VEGFxxxb两者之间的平衡,可作为糖尿病性视网膜病变、年龄相关性黄斑变性等眼内新生血管性疾病的治疗新策略.     

Intraocular cytokines in retinal vein occlusion and its relation to the efficiency of anti-vascular endothelial growth factor therapy

Purpose:To analyze the change in the concentration of intraocular cytokines (ICs) in patients with retinal vein occlusion (RVO) before and after intravitreal ranibizumab therapy (IVR), and to find the correlations of IC with clinical activity of RVO and efficiency of treatment.Results:The levels of 11 cytokines (vascular endothelial growth factor [VEGF], receptor antagonist interleukin-1, interleukin-6 [IL-6], IL-8, IL-9, IL-10, IL-12r70, IL-13, IL-15, monocyte chemotactic protein-1 [MCP-1], regulated on activation, normal T expressed and secreted) were significantly (P < 0.05) different compared to control and significantly (P < 0.05) changed after IVR both in central and branch RVO. The patients were divided into two groups: the first -“effective” and the second - “partially effective” therapy. The second group characterized by the higher concentrations of VEGF, IL-8, IL-10, IL-17, and MCP-1 at baseline compared to the first group.Conclusion:The patients with RVO were characterized by the increased levels of VEGF and other pro- and anti-inflammatory cytokines and chemokines. Aqueous concentration of cytokines were different in patients with central and branch RVO and significantly changed after IVR. Insufficient response to IVR was associated with activation of immune-inflammatory processes.     

Inhibition of corneal neovascularization by topical application of nintedanib in rabbit models

AIM: To evaluate the potential efficacy and mechanisms of nintedanib in corneal neovascularization (NV) in rabbit models. METHODS: Corneal NV was induced using 1 mol/L NaOH. Rabbits (n=21) were randomized to 3 groups: Group 1 were treated with 0.9% NaCl, Group 2 with Avastin (5 mg/mL), and Group 3 with nintedanib (1 mg/mL). All treatments started 1d after alkaline burns and were topically performed 3 times a day for 2wk. Photographs were taken on a slit lamp microscope on day 7 and 14. The NV area, the length of the vascularization and angiogenesis index (AI) were used to evaluate the corneal NV. On day 14, the immunohistochemical (IHC) studies of the cornea were examined. Western blot was performed to test the expression levels of vascular endothelial growth factor (VEGF), Akt, p-Akt, P38, p-P38, MMP-2 and MMP-9. RESULTS: The corneal NV area, vessel length and AI in Group 3 were significantly lower than Group 2, with both being lower than Group 1. IHC staining showed that VEGF was significantly overexpressed in the epithelium and stroma of cornea following alkaline burns. In contrast, the level of VEGF was significantly suppressed in both Group 2 and Group 3. Western blot results further confirmed that, compared with Group 1, Group 3 had significantly reduced expressions of VEGF, Akt, p-Akt, p-P38, MMP-2, and MMP-9 in corneal tissues. Trends of lower levels of MMP-2, AKT, and p-AKT in Group 3 than Group 2 were identified. CONCLUSION: Nintedanib and Avastin can effectively inhibit corneal NV, with P38 MAPK and AKT signaling pathways being possibly involved. Nintedanib seems more effective than Avastin and has the potential to be a novel therapy for preventing corneal NV.     

抗VEGF时代激光视网膜光凝在视网膜静脉阻塞临床管理中的价值

视网膜静脉阻塞(retinal vein occlusion, RVO)是仅次于糖尿病视网膜病变的常见视网膜血管疾病,其视力损害的主要原因是黄斑水肿(macular edema,ME)和眼部新生血管(neovascularition,NV)并发症,尤其是新生血管性青光眼(neovascular glaucoma,NVG)。虽然激光视网膜光凝治疗ME、NV和NVG的疗效早已明确,但抗VEGF治疗可有效改善RVO患者的视力预后,已成为RVO-ME的一线治疗方法,也有助于治疗NV和NVG。近期研究表明,增加激光治疗并不能增加抗VEGF治疗RVO-ME的视力收益,也不能降低抗VEGF注射次数;抗VEGF治疗不能阻止,但可延迟缺血性RVO发生NV并发症。播散性激光视网膜光凝仍是治疗NV并发症的核心方法,但不鼓励预防性激光治疗。(眼科,2022,31:165-168)