Wong Tina T L, Mead Anna L, Khaw Peng T
Wound Healing Research Unit, Department of Pathology, Institute of Ophthalmology, London, United Kingdom.
Invest Ophthalmol Vis Sci. 2003 Mar;44(3):1097-103. doi: 10.1167/iovs.02-0366.
To determine whether postoperative application of a broad-spectrum matrix metalloproteinase (MMP) inhibitor, GM6001 (ilomastat), reduces scarring after glaucoma filtration surgery.
In a randomized, prospective, masked-observer study, 40 New Zealand White rabbits underwent modified glaucoma filtration surgery. The animals were randomly allocated to receive postoperative subconjunctival injections of either phosphate-buffered saline (PBS) or 100 microM ilomastat for 10 days. The animals were killed on days 7, 14, 21, and 30. Clinical characteristics, which included bleb morphology and intraocular pressure, were recorded. Tissue sections were immunohistochemically stained for alpha smooth muscle actin (alphaSMA) and extracellular matrix components in the two groups.
Surgical outcome was significantly prolonged in the ilomastat-treated group compared with the vehicle-treated group (P < 0.001). At day 30, all the blebs had survived except two in the ilomastat-treated group, whereas no blebs survived to day 30 with vehicle treatment (n = 11). The intraocular pressure remained significantly lower throughout the course of the experiment in the ilomastat group compared with the vehicle group (P < 0.0017). Histologically, less scar tissue was observed at the sclerostomy site with inhibition of MMP, compared with vehicle treatment.
The data presented suggest that the healing response after surgery can be modulated by inhibiting the effects of MMPs. Inhibition of MMP significantly improved surgical outcome by reducing the amount of scar tissue produced. By targeting the actions of these proteolytic enzymes, a more controlled and physiological method of modulating scarring may be achieved.
确定术后应用广谱基质金属蛋白酶（MMP）抑制剂GM6001（伊洛马司他）是否能减少青光眼滤过术后的瘢痕形成。
在一项随机、前瞻性、盲法观察研究中，40只新西兰白兔接受改良青光眼滤过手术。动物被随机分配接受术后结膜下注射磷酸盐缓冲盐水（PBS）或100微摩尔伊洛马司他，持续10天。在第7、14、21和30天处死动物。记录包括滤过泡形态和眼压在内的临床特征。对两组组织切片进行α平滑肌肌动蛋白（αSMA）和细胞外基质成分的免疫组织化学染色。
与载体治疗组相比（P < 0.001），伊洛马司他治疗组的手术效果显著延长。在第30天，伊洛马司他治疗组除两只外所有滤过泡均存活，而载体治疗组无滤过泡存活至第30天（n = 11）。在整个实验过程中，伊洛马司他组的眼压与载体组相比仍显著较低（P < 0.0017）。组织学上，与载体治疗相比，MMP受到抑制时在巩膜造口部位观察到的瘢痕组织较少。
所呈现的数据表明，手术愈合反应可通过抑制MMP的作用来调节。抑制MMP通过减少产生的瘢痕组织量显著改善了手术效果。通过靶向这些蛋白水解酶的作用，可以实现一种更可控和生理性的调节瘢痕形成的方法。
