Symonds Joel G, Lovicu Frank J, Chamberlain Coral G
Discipline of Anatomy and Histology and Institute for Biomedical Research, F13, University of Sydney, Sydney, NSW 2006, Australia.
Exp Eye Res. 2006 Oct;83(4):771-82. doi: 10.1016/j.exer.2006.03.017. Epub 2006 May 19.
Posterior capsular opacification (PCO) arises from lens cells that remain associated with the lens capsule after cataract surgery and subsequently become abnormal, proliferate and migrate into the visual pathway. In this study, a rat lens explant model was used to assess the effects of the prototype steroidal and non-steroidal anti-inflammatory drugs, dexamethasone (DEX) and diclofenac (DIC), on epithelial cells undergoing PCO-like changes. Such drugs are widely used at the time of cataract surgery. TGFbeta2 and FGF-2 were added sequentially and explants were cultured for up to 30 days, with or without addition of DEX or DIC at a clinically relevant concentration. Without DEX or DIC, explants became multilayered and cells tended to retract into PCO-like plaques. Inclusion of DEX, but not DIC, resulted in transient formation of needle-like cells, enhanced cell coverage, and the retention a monolayer of migratory cells surrounding PCO-like plaques. With or without drug addition, most cells became aberrant, as indicated by loss of Pax6 expression and the presence of PCO markers alpha-smooth muscle actin and type I collagen; however, DEX and DIC both strongly enhanced type I collagen accumulation. Furthermore, DEX enhanced cell coverage in explants treated with TGFbeta alone. Thus the behaviour of lens cells was significantly and differentially affected by the presence of DEX and DIC, highlighting the possibility that drugs used to control inflammation after cataract surgery, and the clinician's choice of drugs, may influence PCO development.
后囊膜混浊（PCO）源于白内障手术后仍与晶状体囊膜相连的晶状体细胞，这些细胞随后发生异常、增殖并迁移至视觉通路。在本研究中，使用大鼠晶状体外植体模型来评估原型甾体和非甾体抗炎药地塞米松（DEX）和双氯芬酸（DIC）对经历类似PCO变化的上皮细胞的影响。此类药物在白内障手术时广泛使用。依次添加转化生长因子β2（TGFbeta2）和碱性成纤维细胞生长因子-2（FGF-2），并将外植体培养长达30天，添加或不添加临床相关浓度的DEX或DIC。在不添加DEX或DIC的情况下，外植体形成多层结构，细胞倾向于回缩形成类似PCO的斑块。添加DEX而非DIC导致针状细胞短暂形成、细胞覆盖增强，并且在类似PCO的斑块周围保留单层迁移细胞。无论是否添加药物，大多数细胞都出现异常，表现为Pax6表达缺失以及存在PCO标志物α-平滑肌肌动蛋白和I型胶原蛋白；然而，DEX和DIC均强烈增强I型胶原蛋白的积累。此外，DEX增强了仅用TGFbeta处理的外植体中的细胞覆盖。因此，DEX和DIC的存在对晶状体细胞的行为产生了显著且不同的影响，这突出了白内障手术后用于控制炎症的药物以及临床医生对药物的选择可能影响PCO发展的可能性。
