Schultz G S, Strelow S, Stern G A, Chegini N, Grant M B, Galardy R E, Grobelny D, Rowsey J J, Stonecipher K, Parmley V
Department of Obstetrics and Gynecology, University of Florida, Gainesville 32610.
Invest Ophthalmol Vis Sci. 1992 Nov;33(12):3325-31.
Healing of corneal alkali injuries remains a severe clinical challenge. The authors evaluated the effect of a new synthetic inhibitor of matrix metalloproteinases (GM6001 or N-[2(R)-2-(hydroxamido carbonylmethyl)-4-methylpentanoyl]-L-tryptophane methylamide) on preventing ulceration of rabbit corneas after alkali injury. Topical treatment of corneas with severe alkali injuries with 400 micrograms/ml or 40 micrograms/ml GM6001 alone prevented ulceration for 28 days, although 8 of 10 corneas treated with vehicle perforated. Corneas treated with 4 micrograms/ml GM6001 had midstromal depth ulcers. Corneas treated with 400 micrograms/ml of GM6001 contained very few inflammatory cells and had significantly reduced vessel ingrowth compared with vehicle-treated corneas. Epithelial regeneration after moderate alkali injuries also was investigated. Persistent epithelial defects developed 4 days after moderate alkali injury in rabbit corneas treated with vehicle and progressively increased to an average of 20% of the original 6 mm diameter wound by 27 days after moderate alkali injury. By contrast, epithelial regeneration was complete and persisted for 21 days for corneas treated with a formulation containing GM6001 (400 micrograms/ml), epidermal growth factor (10 micrograms/ml), fibronectin (500 micrograms/ml), and aprotinin (400 micrograms/ml). Sporadic punctate staining developed in 20% of the corneas treated with the combination of agents between days 21-28 after moderate alkali injury. These results demonstrate that topical application of GM6001 prevented corneal ulceration after severe alkali injury and that a combination containing GM6001, epidermal growth factor, fibronectin, and aprotinin promoted stable regeneration of corneal epithelium after moderate alkali injury.
角膜碱性损伤的愈合仍然是一个严峻的临床挑战。作者评估了一种新型基质金属蛋白酶合成抑制剂（GM6001或N-[2(R)-2-(羟氨基羰基甲基)-4-甲基戊酰基]-L-色氨酸甲酰胺）对预防兔角膜碱损伤后溃疡形成的效果。单独用400微克/毫升或40微克/毫升GM6001局部治疗重度碱损伤的角膜可预防溃疡形成28天，尽管用赋形剂处理的10只角膜中有8只发生了穿孔。用4微克/毫升GM6001处理的角膜出现基质中层深度溃疡。与用赋形剂处理的角膜相比，用400微克/毫升GM6001处理的角膜含有极少的炎性细胞，血管长入明显减少。还研究了中度碱损伤后的上皮再生情况。在用赋形剂处理的兔角膜中，中度碱损伤后4天出现持续性上皮缺损，并在中度碱损伤后27天逐渐增加至平均为原始6毫米直径伤口的20%。相比之下，用含有GM6001（400微克/毫升）、表皮生长因子（10微克/毫升）、纤连蛋白（500微克/毫升）和抑肽酶（400微克/毫升）的制剂处理的角膜上皮再生完全并持续了21天。在中度碱损伤后21 - 28天，20%用联合制剂处理的角膜出现散在点状染色。这些结果表明，局部应用GM6001可预防重度碱损伤后的角膜溃疡形成，并且含有GM6001、表皮生长因子、纤连蛋白和抑肽酶的联合制剂可促进中度碱损伤后角膜上皮的稳定再生。
