Department of Ophthalmology, University of Lübeck, Ratzeburger Allee 160, Lübeck, Germany.
Graefes Arch Clin Exp Ophthalmol. 2011 Nov;249(11):1649-60. doi: 10.1007/s00417-011-1730-9. Epub 2011 Jul 7.
The cytokine transforming growth factor-ß (TGF-ß) is a pivotal contributor to tissue fibrosis and a key cytokine in the pathogenesis of cellular transdifferentiation, epithelial-mesenchymal transition (EMT), and cell adhesion. This study evaluates the effect of decorin, a naturally occurring TGF-ß inhibitor, in an experimental rabbit model for proliferative vitreoretinopathy (PVR).
Traumatic PVR was induced in 50 rabbits divided into ten groups (n = 5). One group (GI) reveals a control with no treatment after trauma. Groups (GII-GIV) consisted of subgroups receiving phacovitrectomy at three different time points; (a) at the time of trauma, (b) 1 week following trauma, and (c) 2 weeks following trauma. GIII and GIV received 100 μg or 200 μg decorin, respectively. PVR severity was scored from 0 to 4. The amount of fibrosis was quantified using JMicroVision© software.
The control group GI developed severe PVR with tractional retinal detachment (TRD); (PVR score ≥2) in four rabbits out of five. Vitrectomy had a positive effect (p < 0.05) on PVR development when preformed immediately, however the developed fibrosis was high. The best results were obtained when surgery was used in conjunction with decorin that reduced both the PVR score and fibrosis development significantly (p < 0.05). Depending on dosage and time of vitrectomy, PVR could be completely avoided (PVR score = 0) in 16 rabbits out of 30. TRD was prevented in 13 rabbits out of 15 in GIII to 14 rabbits out of 15 in GIV. In decorin-treated eyes, vitrectomy outcome was best when preformed at 1 week after trauma. There were no drug-related toxic effects evident on clinical and histopathological examination.
In conclusion, in this rabbit model of PVR, adjuvant decorin application during vitrectomy effectively reduces fibrosis and TRD development. In conjunction with no obvious histopathological toxicity signs, decorin represents a promising substance to inhibit PVR reactions.
细胞因子转化生长因子-β（TGF-β）是组织纤维化的关键贡献者，也是细胞转分化、上皮-间充质转化（EMT）和细胞黏附发病机制中的关键细胞因子。本研究评估了天然存在的 TGF-β抑制剂——decorin 在增生性玻璃体视网膜病变（PVR）实验性兔模型中的作用。
将 50 只兔子分为 10 组（每组 5 只），造成创伤性 PVR。第 GI 组为未治疗的对照组。第 GII-GIV 组为亚组，分别在创伤时（a）、创伤后 1 周（b）和 2 周（c）行玻璃体切割术。第 GIII 和 GIV 组分别给予 100μg 或 200μg decorin。使用 JMicroVision©软件对 PVR 严重程度进行评分。
对照组 GI 组的 5 只兔子中有 4 只发生严重 PVR 伴牵引性视网膜脱离（TRD）（PVR 评分≥2）。立即行玻璃体切除术对 PVR 发展有积极影响（p<0.05），但纤维化程度较高。当手术与 decorin 联合使用时，效果最佳，可显著降低 PVR 评分和纤维化程度（p<0.05）。根据玻璃体切除术的时间和剂量，在 30 只兔子中有 16 只可完全避免 PVR（PVR 评分=0）。在 GIII 组的 15 只兔子中有 13 只，在 GIV 组的 15 只兔子中有 14 只预防了 TRD。在接受 decorin 治疗的眼睛中，在创伤后 1 周行玻璃体切除术的效果最佳。在临床和组织病理学检查中未发现与药物相关的毒性作用。
总之，在本 PVR 兔模型中，玻璃体切除术中辅助应用 decorin 可有效减少纤维化和 TRD 发展。结合无明显组织病理学毒性迹象，decorin 代表一种有前途的抑制 PVR 反应的物质。
