Lindquist T D, Edenfield M
Department of Ophthalmology, University of Washington, Seattle 98195-0001.
J Refract Corneal Surg. 1994 Mar-Apr;10(2):95-102.
Plasminogen activator has been shown to be released by epithelial cells following corneal injury. The demonstration of the release of plasminogen activator from cultured corneal epithelial cells has been used for developing a cytotoxicity test, the Corneal Epithelial Plasminogen Activator test, which compares changes in the level of plasminogen activator in tissue culture media following chemical exposure as an index of chemical injury.
Cultured rabbit corneal epithelial cells were exposed to varying concentrations of several viscoelastics for 1 hour. Release of plasminogen activator into the tissue culture media following exposure to the viscoelastic agent was studied as an index of chemical injury.
The least cytotoxicity to cultured rabbit epithelium was associated with those viscoelastic agents containing methylcellulose. A 1-hour exposure to most concentrations of methylcellulose and chondroitin sulfate (Phacote) and methylcellulose (Occucoat) demonstrated release of greater amounts of plasminogen activator than was seen following a similar exposure to balanced salt solution, suggesting the greatest protective effect of these two viscoelastics. In contrast, sodium hyaluronate and chondroitin sulfate (Viscoat) showed decreased amounts of plasminogen activator release after a 1-hour exposure to cultured corneal epithelial cells demonstrating cytotoxicity. Polyacrylamide (Orcolon) and most diluted preparations of sodium hyaluronate (Healon and Healon Yellow) showed only mild reductions in the release of plasminogen activator, whereas undiluted sodium hyaluronate preparations were nearly as cytotoxic as Viscoat.
This study suggests that viscoelastic agents containing methylcellulose (Phacote and Occucoat) may be most protective of the corneal epithelium during ophthalmic surgery. The clinical success of several dilute viscoelastic solutions as tear substitutes was corroborated by the lack of cytotoxicity seen in this study. Viscoat and undiluted sodium hyaluronate preparations showed the greatest cytotoxicity to cultured rabbit corneal epithelium.
角膜损伤后，上皮细胞可释放纤溶酶原激活剂。培养的角膜上皮细胞释放纤溶酶原激活剂已被用于开发一种细胞毒性试验，即角膜上皮纤溶酶原激活剂试验，该试验比较化学物质暴露后组织培养基中纤溶酶原激活剂水平的变化，以此作为化学损伤的指标。
将培养的兔角膜上皮细胞暴露于不同浓度的几种粘弹剂中1小时。研究暴露于粘弹剂后纤溶酶原激活剂释放到组织培养基中的情况，以此作为化学损伤的指标。
对培养的兔上皮细胞细胞毒性最小的是含有甲基纤维素的粘弹剂。大多数浓度的甲基纤维素和硫酸软骨素（Phacote）以及甲基纤维素（Occucoat）暴露1小时后，与相似暴露于平衡盐溶液相比，显示出释放出更多的纤溶酶原激活剂，表明这两种粘弹剂具有最大的保护作用。相比之下，透明质酸钠和硫酸软骨素（Viscoat）暴露于培养的角膜上皮细胞1小时后，纤溶酶原激活剂释放量减少，显示出细胞毒性。聚丙烯酰胺（Orcolon）和大多数稀释的透明质酸钠制剂（Healon和Healon Yellow）仅显示纤溶酶原激活剂释放略有减少，而未稀释的透明质酸钠制剂的细胞毒性几乎与Viscoat一样大。
本研究表明，含有甲基纤维素的粘弹剂（Phacote和Occucoat）在眼科手术期间可能对角膜上皮具有最大的保护作用。本研究中观察到的无细胞毒性证实了几种稀释粘弹剂溶液作为泪液替代品的临床成功。Viscoat和未稀释的透明质酸钠制剂对培养的兔角膜上皮细胞显示出最大的细胞毒性。
