缺血-再灌注大鼠视网膜TPA变化与视网膜水肿的关系

目的　探讨缺血-再灌注对大鼠视网膜分泌组织型纤溶酶原激活物(TPA)的影响及其与视网膜水肿的关系。方法　采用提高眼压法造成视网膜缺血后,恢复眼压形成血流再灌注。实验分正常对照组、缺血 1h再灌注 1h组、缺血 1h再灌注 2h组、缺血 2h再灌注 1h组和缺血 2h再灌注 2h组。每组各取 10例测试视网膜组织TPA的活性和含水量。结果　缺血-再灌注后,大鼠视网膜组织TPA的活性和含水量随缺血和再灌注时间的延长而升高(P<0 01)。 结论　缺血-再灌注可引起视网膜组织TPA的活性升高和视网膜水肿,是视网膜组织结构和功能损伤的因素之一。     

Influence of retinal ischemia on macular function after pars plana vitrectomy for macular edema with branch retinal vein occlusion

The influence of retinal ischemia on changes of visual acuity, macular sensitivity, macular thickness, and macular volume is unclear after pars plana vitrectomy (PPV) for macular edema with branch retinal vein occlusion (BRVO). Twenty-three patients (23 eyes) with BRVO and macular edema underwent PPV. Retinal ischemia was evaluated from capillary non-perfusion on fluorescein angiography, and patients were classified as ischemic or nonischemic. Microperimetry was performed with a Micro Perimeter 1. Macular thickness and volume were measured by optical coherence tomography. Mean macular thickness within the central 4°, 10°, and 20° fields decreased significantly from before to 3 and 6 months after PPV (all P < 0.001). Likewise, total macular volume within the central 4°, 10°, and 20° fields decreased significantly from before to 3 and 6 months after PPV (all P < 0.001). Best-corrected visual acuity (BCVA) improved significantly from before to 3 and 6 months after PPV (P < 0.001). Furthermore, mean macular sensitivity within the central 4°, 10°, and 20° fields increased significantly from before to 3 and 6 months after PPV (P = 0.002, P = 0.001, and P = 0.001, respectively). There were no significant differences in the trend profiles of macular thickness, macular volume, and BCVA between the ischemic and nonischemic groups. However, there was a significant difference in the trend profile of macular sensitivity within the central 4°, 10°, and 20° fields between the ischemic and nonischemic groups (P = 0.017, P = 0.010 and P = 0.025, respectively). These findings suggest PPV may be more effective for improving macular sensitivity in ischemic than nonischemic BRVO.     

Progression of diabetic macular edema: correlation with blood retinal barrier permeability, retinal thickness, and retinal vessel diameter

PURPOSE: To study the progression of diabetic macular edema (DME) in relation to baseline retinal thickness, retinal vascular leakage, and retinal trunk vessel diameters. METHODS: In this single-center study, 45 patients were enrolled with 62 eligible eyes defined as having DME of a grade less than clinically significant macular edema (CSME). From the start, the patients were included in a multicenter study exploring the effect of ruboxistaurin versus placebo for 3.4 years. Subsequently, the patients were followed up for a mean of 5.7 years by optical coherence tomography, fundus photography, and vitreous fluorometry. Baseline values in eyes that progressed to photocoagulation treatment were compared with values from eyes that did not reach this endpoint. RESULTS: In the 22 eyes of 18 patients in which CSME was diagnosed and treated, mean retinal vascular leakage at baseline was 5.6 (95% CI 4.2-7.6) nm/s, whereas eyes that did not progress to photocoagulation had a significantly lower mean leakage at baseline of 3.4 (95% CI 2.7-4.3) nm/s. No significant difference was found for measures of baseline retinal thickness or summarized retinal trunk vessel diameters. Eyes that progressed to photocoagulation treatment (mean delay to treatment, 3.6 years) had significantly higher foveal thicknesses than did nonprogressing eyes, from 18 months after study initiation. CONCLUSIONS: Progression to photocoagulation treatment for CSME was associated with higher retinal vascular leakage at baseline, whereas baseline retinal vessel diameters and retinal thickness were comparable in progressing and nonprogressing eyes. Baseline leakage was the strongest predictor of progression from non-CSME to photocoagulation for CSME.     

Mechanisms of fluid accumulation in retinal edema

This paper reviews the anatomic and physiologic conditions which predispose to fluid accumulation within the retina. Retinal edema has its inception in disease that causes a breakdown of the blood-retinal barrier in retinal capillaries and/or the retinal pigment epithelium (RPE). Edema develops not only because protein and fluid enter the extracellular space, but because the external limiting membrane and the convoluted extracellular pathway within the retina limit the clearance of albumin and other large osmotically-active molecules. These molecules bind water to cause edema. Recognition of edema clinically is complicated by the facts that angiographic markers (fluorescein and ICG) do not match albumin in size, and that clinical leakage does not always correlate closely with tissue swelling or functional loss. Active water transport across the RPE is efficient at removing subretinal water, but the flow resistance of the retina limits RPE access to the water of retinal edema. Consideration of the pathophysiology of retinal edema may aid in the development of better strategies for managing retinal edema. This revised version was published online in July 2006 with corrections to the Cover Date.     

Quercetin inhibits choroidal and retinal angiogenesis in vitro

Background Quercetin is a natural substance found abundantly in grapes, red wine and other food products. In this study, we examined the effect of quercetin on choroidal and retinal angiogenesis in vitro using rhesus choroids-retina endothelial cell line (RF/6A). Methods RF/6A cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) containing 10% fetal bovine serum. Then cells were treated with different concentrations (from 0 to 100 μM) of quercetin. The cell proliferation was assessed using choromogenic methylthiazol tetrazolium bromide (MTT) dye after 24, 48 and 72 hours. Cell migration after 24-hour incubation with quercetin was investigated by wound assay. Following exposure to the various concentrations of quercetin for 24 hours, tube formation on matrigel by endothelial cells was also analyzed. Apoptosis was measured by flow cytometry using annexin V-FITC and propidium iodide staining. Results Quercetin inhibits endothelial cell proliferation in a dose-dependent fashion; 10.1%, 42.6% and 65.2% inhibition on treating with 10, 50 and 100 μM Quercetin respectively. The migration and tube formation of RA/6A cells were also significantly inhibited by quercetin in a dose-dependent manner. Flow cytometric analysis showed that the percentages of apoptotic cells were slightly increased only in 100 μM quercetin-treated cells. Conclusions Our results show that quercetin inhibits choroidal and retinal angiogenesis in vitro. Further studies are ongoing to evaluate this drug as a potential candidate for the treatment of choroidal or retinal neovascularization.     

PEDF抑制鼠视网膜新生血管的实验研究(英文)

目的:观察PEDF对氧诱导的血管增生性视网膜病变动物模型视网膜新生血管的抑制作用。方法:40只7日龄的C57BL/6J新生鼠暴露在750mL/L高氧环境中,然后回到正常空气中建立氧诱导的血管增生性视网膜病变的动物模型。随机取1眼为实验眼,在出氧箱时(12d)玻璃体腔注射PEDF,另1眼为对照组,玻璃体腔注射PBS。所有小鼠均于17d处死,视网膜铺片,ADP酶染色观察视网膜血管情况。HE染色,在光学显微镜下观察并计数突破视网膜内界膜的血管内皮细胞细胞核数目。结果:与对照组相比,实验组视网膜血管分布规则,未见明显的无灌注区形成;实验组突破内界膜的内皮细胞细胞核数目(10.18±1.74)比对照组(38.89±2.98)明显减少(P<0.01) ;组织切片未见视网膜毒性及炎症反应。结论:PEDF能够有效抑制视网膜新生血管的生成。     

PlGF-1 and VEGFR-1 pathway regulation of the external epithelial hemato-ocular barrier. A model for retinal edema

VEGF is considered as an important factor in the pathogenesis of macular edema. VEGF induces the rupture of the blood retinal barrier and may also influence the retinal pigment epithelial (RPE) outer retinal barrier. The aim of this work was to analyze the influence of the VEGF receptor pathways in the modulation of the RPE barrier breakdown in vitro and in vivo. The ARPE19 human junctions in culture are modulated by VEGF through VEGFR-1 but not through VEGFR-2. PlGF-1, that is a pure agonist of VEGFR-1, is produced in ARPE-19 cells under hypoxic conditions and mimics VEGF effects on the external retinal barrier as measured by TER and inulin flux. In vivo, the intravitreous injection of PlGF-1 induces a rupture of the external retinal barrier together with a retinal edema. This effect is reversible within 4 days. VEGF-E, that is a pure agonist of VEGFR-2, does not induce any acute effect on the RPE barrier. These results demonstrate that PlGF-1 can reproduce alterations of the RPE barrier occurring during diabetic retinopathy.     

Inhibition of retinal angiogenesis by PEDF

AIM: To investigate the effect of PEDF on retinal neovascularization in mice. METHODS: 40 7-day-old C57BL/6J mice was exposed to 750mL/L oxygen for 5 days and then to normal situation to produce the murine model of oxygen-induced retinopathy(OIR). One eye of the mouse was regarded as experimental one and the other served as control. Eyes in experimental group received intravitreal injection of PEDF and eyes in control group received intravitreal injection of PBS at postnatal day 12. All mice were executed at postnatal day 17. The changes of retinal vessels of mice were observed by ADPase histochemical technique. The inhibitory effect of PEDF on retinal neovascularization was evaluated by counting the endotheliocyte nuclei of new vessels which extended from retina to vitreous in the tissue slice of HE staining. RESULTS: Neovascularization was reduced, retinal blood vessels distributed regularly and non-perfusion areas were not found in eyes of experimental group compared with control group. The number of endotheliocyte nuclei of new vessels extending from retina to vitreous was significantly less in the eyes of experimental group (10.18±1.74) than that in control group (38.89±2.98) (P <0.01). Retinal toxicity and inflammatory reactions were not found in tissue slice. CONCLUSION: PEDF inhibits retinal angiogenesis in OIR and the feasibility should be determined for use of PEDF in ocular angiogenesis treatment.     

小胶质细胞在视网膜血管生成中的作用机制研究进展

视网膜小胶质细胞作为视网膜的常驻免疫细胞,不断监测其周围环境的变化,并通过与其他视网膜细胞的信号传导维持稳态。视网膜小胶质细胞不仅在视网膜血管系统的发育和生理过程中发挥重要作用,而且在病理性新生血管形成中也起着至关重要的作用。在某些视网膜病变中,活化的小胶质细胞通过神经血管耦联,促进异常血管生成,从而造成不可逆的损伤,但具体的作用机制尚不明确。本文简要综述小胶质细胞与视网膜新生血管生成的相关性,并讨论了参与该过程的细胞和分子信号机制,旨在为视网膜新生血管性疾病的预防和治疗提供新的有效的策略。     

Innovations in the treatment of the macular edema in retinal venous occlusions

The authors present new possibilities in the treatment of the macular edema caused by the retinal venous occlusions; these occlusions are the second most common retinal vessel disease. The earlier possibilities of the treatment were focused on the macular edema laser treatment, laser panretinal photocoagulation in case of retinal or iris neovascularization presence, and the disease's risk factors compensation. In the presence, the intravitreal application of corticosteroids or anti VEGF A preparations are more used for the treatment because of better results, as proved by means of randomized, clinical studies.     

激光对水肿视网膜的生物效应

目的：初步研究激光对水肿视网膜的生物效应。方法：在视网膜静脉阻塞的动物模型上采用三种不同波长的激光(氩离子、半导体和532倍频)对水肿视网膜进行光凝。光凝后即刻和7天行眼底彩色照相，并在光、电镜下观察水肿视网膜的组织病理学及超微结构改变。结果：半导体光凝斑可造成视网膜色素上皮细胞增生、游离进入视网膜外核层，严重者达内核层；少数氩离子光凝斑可见轻度色素上皮层细胞紊乱。但各波长激光光凝水肿视网膜后，Bruch氏膜都始终保持完整。结论：眼底可见的传统概念边界清晰的乳白色视网膜光凝反应对于水肿视网膜己为过强，要在水肿视网膜上达到与正常视网膜光凝后相对序的组织学改变，其所呈现的反应应较正常的轻。