Eibl K H, Lewis G P, Betts K, Linberg K A, Gandorfer A, Fisher S K, Kampik A
Augenklinik der Ludwig-Maximilians-Universität, Mathildenstrasse 8, 80336, München.
Ophthalmologe. 2007 Nov;104(11):972-7. doi: 10.1007/s00347-007-1574-1.
Proliferative vitreoretinopathy (PVR) is a major complication after retinal detachment surgery, but there is no established pharmacotherapy available to control the cell biology of the disease. The aim of this study was to investigate the role of alkylphosphocholines [APCs; erucylphosphocholine (ErPC) was used in this study], novel pharmacologic substances with antiproliferative properties, on intraretinal proliferation initiated by experimental retinal detachment in a well-established in vivo model.
Retinal detachments were created in adult pigmented rabbits. ErPC was injected intravitreally on either day 1 or day 2 after detachment. Bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU) was injected on day 3. Following fixation, retinas were triple-labelled with anti-BrdU (proliferation marker), Isolectin B4 (retinal microglia marker), and anti-vimentin (retinal Mueller glia cell marker). The number of anti-BrdU-labelled cells per millimeter of retina was determined from sections imaged by laser scanning confocal microscopy. Toxicity was assessed by light and electron microscopy.
A single intravitreal injection of ErPC had a significant effect on reducing the number of proliferating non-neural retinal cells on day 3 after experimental retinal detachment in the rabbit. Injection of ErPC on day 1 was more effective than when given on day 2. No evidence of toxicity was observed in the retina on day 3 for any of the conditions.
APCs are novel pharmacologic substances that significantly inhibited intraretinal proliferation after experimental retinal detachment in this in vivo model. They could be considered as an adjunct therapy at the time of retinal reattachment surgery to potentially prevent proliferative vitreoretinal diseases such as PVR. However, long-term toxicity studies must be performed before APCs can be considered for clinical application.
增殖性玻璃体视网膜病变（PVR）是视网膜脱离手术后的一种主要并发症，但目前尚无成熟的药物疗法可用于控制该疾病的细胞生物学过程。本研究的目的是在一个成熟的体内模型中，研究具有抗增殖特性的新型药物烷基磷胆碱[APCs；本研究中使用的是芥酸磷胆碱（ErPC）]对实验性视网膜脱离引发的视网膜内增殖的作用。
在成年有色家兔中制造视网膜脱离。在脱离后的第1天或第2天经玻璃体注射ErPC。在第3天注射溴脱氧尿苷（5-溴-2-脱氧尿苷，BrdU）。固定后，用抗BrdU（增殖标记物）、荆豆凝集素B4（视网膜小胶质细胞标记物）和抗波形蛋白（视网膜穆勒胶质细胞标记物）对视网膜进行三重标记。通过激光扫描共聚焦显微镜成像的切片确定每毫米视网膜中抗BrdU标记细胞的数量。通过光学和电子显微镜评估毒性。
单次玻璃体注射ErPC对减少家兔实验性视网膜脱离后第3天增殖的非神经视网膜细胞数量有显著作用。在第1天注射ErPC比在第2天注射更有效。在第3天，任何条件下均未在视网膜中观察到毒性证据。
在这个体内模型中，APCs是新型药物，可显著抑制实验性视网膜脱离后的视网膜内增殖。它们可被视为视网膜复位手术时的辅助治疗，以潜在预防诸如PVR等增殖性玻璃体视网膜疾病。然而，在考虑将APCs用于临床应用之前，必须进行长期毒性研究。
