Mietz H, Chévez-Barrios P, Lieberman M W, Wendt M, Gross R, Basinger S F
Department of Pathology, Baylor College of Medicine, Houston, Texas, USA.
Graefes Arch Clin Exp Ophthalmol. 1997 Jun;235(6):399-403. doi: 10.1007/BF00937291.
The process of ocular wound healing with respect to glaucomatous filtering procedures is of current interest. Delaying this response in patients could possibly lead to more favorable surgical results. So far, only highly toxic antimetabolites have come into frequent clinical use. The possible efficacy of other groups of substances such as growth factor inhibitors has not yet been examined in vitro.
We exposed Tenon's capsule fibroblasts in tissue culture to various concentrations of decorin and suramin. The dose responses of type I and type III collagen to these inhibitors were measured using an ELISA-type dot blot assay. Total cellular protein production was assayed by measuring the incorporation of tritiated leucine.
At a concentration of 10 micrograms/ml, suramin reduced the collagen production by more than 80%. Decorin, at a concentration of 100 micrograms/ml, reduced type I collagen production by about 50% while type III collagen was reduced by 80%. At these concentrations, the total cellular protein production was not inhibited.
Both suramin and decorin, which specifically inhibit the action of growth factors on target cells, reduce the production of collagen synthesis by Tenon's capsule fibroblasts. This is a specific effect, because total protein production is not influenced. This sets these substances apart from antimetabolites. Decorin and suramin may have clinical relevance in that they appear to interfere with ocular wound healing more specifically than the substances so far frequently used.
青光眼滤过手术相关的眼伤口愈合过程是当前研究的热点。延缓患者的这种反应可能会带来更理想的手术效果。到目前为止,只有高毒性的抗代谢物在临床中频繁使用。其他物质组如生长因子抑制剂的潜在疗效尚未在体外进行研究。
我们将组织培养中的Tenon囊成纤维细胞暴露于不同浓度的核心蛋白聚糖和苏拉明中。使用酶联免疫吸附测定(ELISA)型斑点印迹法测量I型和III型胶原对这些抑制剂的剂量反应。通过测量氚标记亮氨酸的掺入量来测定总细胞蛋白产量。
在浓度为10微克/毫升时,苏拉明使胶原产量降低了80%以上。在浓度为100微克/毫升时,核心蛋白聚糖使I型胶原产量降低约50%,而III型胶原降低80%。在这些浓度下,总细胞蛋白产量未受抑制。
苏拉明和核心蛋白聚糖均能特异性抑制生长因子对靶细胞的作用,降低Tenon囊成纤维细胞的胶原合成产量。这是一种特异性效应,因为总蛋白产量未受影响。这使这些物质有别于抗代谢物。核心蛋白聚糖和苏拉明可能具有临床相关性,因为它们似乎比目前常用的物质更能特异性地干扰眼伤口愈合。