Cordeiro M F, Reichel M B, Gay J A, D'Esposita F, Alexander R A, Khaw P T
Department of Pathology, Moorfields Eye Hospital and Institute of Ophthalmology, London, United Kingdom.
Invest Ophthalmol Vis Sci. 1999 Aug;40(9):1975-82.
To compare the effects of the three human isoforms of transforming growth factor (TGF)-beta in vivo using a mouse model of conjunctival scarring, both in normal eyes and after treatment with MMC, with a view to delineating the role of this growth factor in glaucoma filtration surgery.
Application of recombinant human TGF-beta was assessed in a prospective, randomized study of mouse conjunctival scarring, in which subconjunctival TGF-beta1, -beta2, and -beta3 (all 10(-9) M) were compared with control (phosphate-buffered saline [PBS] carrier) and mitomycin C (MMC; 0.4 mg/ml) treatment at 6 hours, and 1, 3, and 7 days after surgery (six eyes/treatment/time point). Effects of TGF-beta2 on eyes previously treated with MMC were also assessed. Histologic studies of enucleated eyes were performed to analyze development of the scarring response, extracellular matrix deposition, and the inflammatory cell profile.
All three isoforms of TGF-beta behaved in a similar manner in vivo, being associated with a rapid-onset and exaggerated scarring response compared with control and MMC treatment. TGF-beta-treated eyes showed evidence of an earlier peak in inflammatory cell activity (P < 0.05) and increased collagen type III deposition (P < 0.05). TGF-beta2 treatment significantly stimulated scarring after MMC application (P < 0.05).
TGF-beta1, -beta2, and -beta3 appear to have similar actions in vivo and stimulate the conjunctival scarring response. Application of TGF-beta2 modified the effects of MMC. All TGF-beta isoforms may be potent modulators of the conjunctival scarring response. These studies indicate that TGF-beta2 may naturally modify the antiscarring effects of antimetabolites such as MMC in glaucoma filtration surgery.
使用结膜瘢痕形成的小鼠模型，比较三种人转化生长因子（TGF）-β 异构体在正常眼以及丝裂霉素 C（MMC）治疗后的体内作用，以明确该生长因子在青光眼滤过手术中的作用。
在一项关于小鼠结膜瘢痕形成的前瞻性随机研究中，评估重组人 TGF-β 的应用情况，将结膜下注射 TGF-β1、-β2 和 -β3（均为 10⁻⁹ M）与对照组（磷酸盐缓冲盐水 [PBS] 载体）以及在术后 6 小时、1、3 和 7 天使用丝裂霉素 C（MMC；0.4 mg/ml）治疗进行比较（每组六个眼/治疗/时间点）。还评估了 TGF-β2 对先前用 MMC 治疗过的眼睛的影响。对摘除的眼睛进行组织学研究，以分析瘢痕形成反应的发展、细胞外基质沉积和炎症细胞谱。
TGF-β 的所有三种异构体在体内表现出相似的行为，与对照组和 MMC 治疗相比，与快速发作且过度的瘢痕形成反应相关。TGF-β 处理的眼睛显示出炎症细胞活性更早达到峰值的证据（P < 0.05）和 III 型胶原沉积增加（P < 0.05）。TGF-β2 治疗在应用 MMC 后显著刺激瘢痕形成（P < 0.05）。
TGF-β1、-β2 和 -β3 在体内似乎具有相似的作用，并刺激结膜瘢痕形成反应。TGF-β2 的应用改变了 MMC 的作用。所有 TGF-β 异构体可能都是结膜瘢痕形成反应的有效调节剂。这些研究表明，在青光眼滤过手术中，TGF-β2 可能自然地改变抗代谢药物如 MMC 的抗瘢痕作用。
