The Cole Eye Institute, The Cleveland Clinic, Cleveland, OH, USA.
Department of Ophthalmology at University of Sao Paulo, Sao Paulo, Brazil.
Transl Vis Sci Technol. 2024 Aug 1;13(8):22. doi: 10.1167/tvst.13.8.22.
The purpose of this study was to evaluate the safety and efficacy of topical losartan in the therapeutic treatment of established corneal scaring fibrosis at 1 month after alkali burn in rabbits.
Standardized alkali burns were performed in 1 eye of 24 rabbits with 0.75N NaOH for 15 seconds. Corneas were allowed to heal and develop scaring of the cornea for 1 month. Twelve eyes per group were treated with 50 µL of topical 0.8 mg/mL losartan in balanced salt solution (BSS), pH 7.0, and 12 eyes were treated with vehicle BSS 6 times per day. Six corneas were analyzed at 1 week or 1 month in each group. Standardized slit lamp photographs were obtained at the end point for each cornea and opacity was quantitated using ImageJ. Corneoscleral rims were cryofixed in optimum cutting temperature (OCT) solution and combined duplex immunohistochemistry for myofibroblast marker alpha-smooth muscle actin (α-SMA), mesenchymal cell marker vimentin, and TUNEL assay for apoptosis was performed on all corneas.
Topical losartan was effective in the treatment of established stromal fibrosis following alkali burn injury to the rabbit cornea. Stromal myofibroblast density was decreased and stromal cell apoptosis was increased (included both α-SMA-positive myofibroblasts and α-SMA-negative, vimentin-positive cells) at both 1 week and 1 month in the topical losartan-treated compared with vehicle-treated groups.
Topical losartan is effective in the treatment of established stromal fibrosis in rabbits. Most myofibroblasts disappear from the stroma within the first month of losartan treatment. Longer treatment with topical losartan is needed to allow time for corneal fibroblast regeneration of the epithelial basement membrane (in coordination with epithelial cells) and the removal of disordered extracellular matrix produced by myofibroblasts.
本研究旨在评估局部应用氯沙坦治疗兔碱性烧伤 1 个月后角膜瘢痕纤维化的安全性和有效性。
用 0.75N NaOH 将 24 只兔的 1 只眼标准化碱烧伤 15 秒。允许角膜愈合并在 1 个月后形成角膜瘢痕。每组 12 只眼用 50 μL 局部 0.8mg/mL 氯沙坦平衡盐溶液（BSS）治疗，pH 值为 7.0，12 只眼每天用载体 BSS 治疗 6 次。每组 6 只眼角膜在 1 周或 1 个月时进行分析。用标准裂隙灯照相术获取每个角膜的终点照片，并使用 ImageJ 定量混浊度。用最优切割温度（OCT）溶液冷冻角膜巩膜边缘，并对所有角膜进行肌成纤维细胞标志物α-平滑肌肌动蛋白（α-SMA）、间充质细胞标志物波形蛋白的双重免疫组织化学和 TUNEL 凋亡检测。
局部应用氯沙坦可有效治疗兔角膜碱烧伤后形成的基质纤维化。与载体治疗组相比，局部应用氯沙坦治疗组的基质肌成纤维细胞密度降低，基质细胞凋亡增加（包括α-SMA 阳性肌成纤维细胞和α-SMA 阴性、波形蛋白阳性细胞），无论是在 1 周还是 1 个月时。
局部应用氯沙坦可有效治疗兔角膜基质纤维化。在接受氯沙坦治疗的前 1 个月内，大多数肌成纤维细胞从基质中消失。需要更长时间的局部应用氯沙坦，以便为角膜成纤维细胞再生上皮基底膜（与上皮细胞协调）和清除肌成纤维细胞产生的无序细胞外基质提供时间。
