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环孢素A-装载的纳米纤维治疗碱损伤角膜-另一种治疗模式

Cejkova J, Cejka C, Trosan P, et al.

期刊名称:Experimental Eye Research

卷期:2016年第146卷

关键词:
角膜 纳米 纤维

摘要

本研究试图研发一种新的方法来抑制碱损伤兔角膜的炎症及新生血管。为此,研究人员将环孢素ACSA)纳米纤维用在碱(氢氧化钠0.25N)损伤眼表面。将受损角膜分为以下几组:未经治疗组,环孢素滴眼液治疗组,不含药物的纳米纤维治疗组和含环孢素A的纳米纤维治疗组。将健康兔眼角膜作为对照。碱损伤后立即将不含药物的纳米纤维和CSA纳米纤维用于受损的角膜表面并缝合至结膜。损伤后第5天,去除纳米纤维。损伤后12天处死各组动物。对炎症反应和角膜愈合程度进行了肉眼,免疫组织化学和生物化学检查。使用超声波测厚计测量中央角膜厚度。当比较未治疗的受损角膜,不含环孢素的纳米纤维治疗的受损角膜和含有环孢素滴眼液的纳米纤维治疗的受损角膜时,含有环孢素的纳米纤维治疗角膜的CD3阳性细胞(T淋巴细胞)的数量和促炎性细胞因子的生成明显减少,基质金属蛋白酶9,诱导型一氧化氮合酶,血管内皮生长因子和活性胱天蛋白酶-3的表达显著下降。环孢素纳米纤维可有效抑制角膜炎症和角膜新生血管。仅含有环孢素的纳米纤维治疗角膜的中央角膜厚度恢复到受损前水平。这些角膜的透明度高度恢复。这显示,环孢素纳米纤维的有益作用与环孢素A从纳米纤维中持续释放和和环孢素A持续作用于受损角膜有关。纳米纤维缝合至结膜和闭眼有利于角膜愈合。总之,环孢素A纳米纤维法可代表治疗角膜化学灼伤的一种有效的替代方式。

In this study we tried to develop a new approach to suppress inflammation and neovascularization in the alkali-injured rabbit cornea. For this reason Cyclosporine A (CsA)-loaded electrospun nanofibers were transferred onto the ocular surface injured with alkali (0.25N NaOH). Damaged corneas were divided into the following groups: untreated, treated with CsA eye drops, treated with nanofibers drug-free and treated with CsA-loaded nanofibers. Healthy rabbit corneas served as controls. Drug-free nanofibers and CsA-loaded nanofibers were transferred onto the damaged corneal surface immediately after the injury and sutured to conjunctiva. On day five after the injury the nanofibers were removed. The animals from all groups were sacrificed on day twelve after the injury. The extent of the inflammatory reaction and corneal healing were examined macroscopically, immunohistochemically and biochemically. The central corneal thickness was measured using an ultrasonic pachymeter. When compared with untreated injured corneas, injured corneas treated with drug-free nanofibers or injured corneas treated with CsA eye drops, the number of CD3-positive cells (T lymphocytes) and the production of pro-inflammatory cytokines were strongly reduced in corneas treated with CsA-loaded nanofibers, which was associated with the significantly decreased expression of matrix metalloproteinase 9, inducible nitric oxide synthase, vascular endothelial growth factor and active caspase-3. CsA-loaded nanofibers effectively suppressed corneal inflammation and corneal neovascularization. Central corneal thickness restored to levels before injury only in corneas treated with CsA-loaded nanofibers. Corneal transparency was highly restored in these corneas. It is suggested that the beneficial effect of CsA-loaded nanofibers was associated with the continuous release of CsA from nanofibers and continuous affection of damaged cornea by CsA. The suture of nanofibers to conjunctiva and the closed eyes contributed to beneficial corneal healing. This is in contrast to CsA eye drops, which are quickly washed from the ocular surface and the contact of CsA with the damaged cornea was limited. In conclusion, the approach with CsA-loaded nanofibers could represent an effective alternative mode of therapy for corneal chemical burns.

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