Posterior vitreous detachment with microplasmin alters the retinal penetration of intravitreal bevacizumab (Avastin) in rabbit eyes.
Posterior vitreous detachment with microplasmin alters the retinal penetration of intravitreal bevacizumab (Avastin) in rabbit eyes.
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DOI：
10.1097/iae.0b013e3181e586b2
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发表时间：
2011-02
期刊：
影响因子：
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通讯作者：
Ruby AJ
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文献类型：
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作者：
Goldenberg DT;Giblin FJ;Cheng M;Chintala SK;Trese MT;Drenser KA;Ruby AJ
玻璃体内注射贝伐单抗（Avastin）常用于治疗年龄相关性黄斑变性。先前的研究已经证明了全层视网膜穿透。玻璃体内重组微纤溶酶（MP）已被证明成功地诱导玻璃体后脱离（PVD）和玻璃体液化的动物。已经提出PVD可以改变玻璃体腔中的分子的视网膜穿透。本研究的目的是比较贝伐珠单抗（BV）在存在和不存在MP诱导的PVD的兔眼中的视网膜渗透。12只成年家兔的一只眼玻璃体腔内注射0.1ml（0.4mg）MP。一周后，兔双眼注射BV 0.05 ml（1.25 mg）。分别在BV注射后6、12、24和72小时收获3只兔的双眼。制备冰冻视网膜横截面，并使用针对BV的荧光标记抗体通过免疫组织化学评价BV视网膜渗透。一只兔子的两只眼睛没有注射任何一种试剂，并用作对照以比较背景自体荧光。用数码相机记录视网膜乳头周围切片，并通过定性摄影判读测量视网膜内BV荧光标记抗体。另外两只兔子的一只眼睛接受了0.1 ml MP的玻璃体内注射。一周后，摘除每只兔的双眼，制备冷冻视网膜切片，并用光学显微镜分析，以评价组织学损伤。在每只家兔的双眼中，在整个视网膜中观察到全层BV视网膜穿透。与对侧未注射MP的眼睛相比，所有注射MP的眼睛在BV注射后6、12和24小时评价的视网膜中显示出增加的抗体标记。BV注射后3天，所有眼睛的抗体标记与早期相比均降低。在第三天，与对侧MP注射眼相比，一只兔子在非MP注射眼的视网膜中显示出增加的抗体标记，两只兔子在双眼中显示出相似的抗体标记。与对照眼相比，光学显微镜检查显示仅注射微纤溶酶的眼的视网膜组织学结果正常。最初在患有MP诱导的PVD的眼睛中观察到BV视网膜穿透增加，其机制可能是多因素的。到第三天，视网膜穿透在有和没有PVD的眼睛中相似。虽然很难直接外推到人类，但我们的研究表明PVD可能会改变BV的视网膜渗透。
Intravitreal bevacizumab (Avastin) is frequently used for the treatment of age-related macular degeneration. Previous studies have demonstrated full thickness retinal penetration. Intravitreal recombinant microplasmin (MP) has been shown to successfully induce a posterior vitreous detachment (PVD) and vitreous liquefaction in animals. It has been suggested that a PVD may alter the retinal penetration of molecules in the vitreous cavity. The aim of this study was to compare bevacizumab (BV) retinal penetration in rabbit eyes with and without a MP-induced PVD. Twelve adult rabbits were injected with 0.1 ml (0.4 mg) of MP into the vitreous cavity of one eye. One week later, the rabbits were injected with 0.05 ml (1.25 mg) of BV into both eyes. Both eyes of three rabbits each were harvested at 6, 12, 24, and 72 hours after the BV injection. Frozen retinal cross sections were prepared, and BV retinal penetration was evaluated with immunohistochemistry using a fluorescence-labeled antibody against BV. Two eyes from one rabbit were not injected with either agent and used as controls to compare the background autofluorescence. Peripapillary retinal sections were recorded with a digital camera, and intra-retinal BV fluorescence-labeled antibody was measured by qualitative photographic interpretation. Two additional rabbits received an intravitreal injection of 0.1 ml of MP in one eye. One week later, both eyes from each rabbit were enucleated and frozen retinal sections were prepared and analyzed with light microscopy to evaluate for histologic damage. Full thickness BV retinal penetration was observed throughout the retina in both eyes of each rabbit. All of the MP-injected eyes exhibited increased antibody labeling in retinas evaluated 6, 12, and 24 hours after BV injection when compared with the contralateral non-MP-injected eyes. By three days after BV injection, all eyes demonstrated decreased antibody labeling compared to earlier time periods. At three days, one rabbit showed increased antibody labeling in the retina of the non-MP-injected eye compared with the contralateral MP-injected eye, and two rabbits exhibited similar antibody labeling in both eyes. When compared with control eyes, light microscopy demonstrated normal retinal histologic findings in eyes injected only with microplasmin. Increased BV retinal penetration is observed initially in eyes with a MP-induced PVD, and the mechanism is likely multifactorial. By three days, retinal penetration is similar in eyes with and without a PVD. Although it is difficult to directly extrapolate to humans, our study suggests a PVD may alter the retinal penetration of BV.