Department of Ophthalmology, Schepens Eye Research Institute of Mass Eye and Ear, Harvard Medical School, Boston, MA, USA.
Sci Rep. 2022 Jan 11;12(1):494. doi: 10.1038/s41598-021-04418-x.
Keratitis induced by bacterial toxins, including lipopolysaccharide (LPS), is a major cause of corneal opacity and vision loss. Our previous study demonstrates hepatocyte growth factor (HGF) promotes epithelial wound healing following mechanical corneal injury. Here, we investigated whether HGF has the capacity to suppress infectious inflammatory corneal opacity using a new model of LPS-induced keratitis. Keratitis, induced by two intrastromal injections of LPS on day 1 and 4 in C57BL/6 mice, resulted in significant corneal opacity for up to day 10. Following keratitis induction, corneas were topically treated with 0.1% HGF or PBS thrice daily for 5 days. HGF-treated mice showed a significantly smaller area of corneal opacity compared to PBS-treated mice, thus improving corneal transparency. Moreover, HGF treatment resulted in suppression of α-SMA expression, compared to PBS treatment. HGF-treated corneas showed normalized corneal structure and reduced expression of pro-inflammatory cytokine, demonstrating that HGF restores corneal architecture and immune quiescence in corneas with LPS-induced keratitis. These findings offer novel insight into the potential application of HGF-based therapies for the prevention and treatment of infection-induced corneal opacity.
细菌毒素（包括脂多糖 [LPS]）引起的角膜炎是导致角膜混浊和视力丧失的主要原因。我们之前的研究表明，肝细胞生长因子 (HGF) 可促进机械性角膜损伤后的上皮伤口愈合。在这里，我们使用新的 LPS 诱导性角膜炎模型研究了 HGF 是否具有抑制感染性炎症性角膜混浊的能力。在 C57BL/6 小鼠中，通过在第 1 天和第 4 天两次在基质内注射 LPS 诱导角膜炎，导致角膜混浊长达 10 天。角膜炎诱导后，用 0.1% HGF 或 PBS 每天 3 次局部治疗 5 天。与 PBS 处理的小鼠相比，HGF 处理的小鼠的角膜混浊面积明显较小，从而提高了角膜透明度。此外，与 PBS 处理相比，HGF 处理导致 α-SMA 表达受到抑制。HGF 处理的角膜表现出正常的角膜结构和减少的促炎细胞因子表达，表明 HGF 可恢复 LPS 诱导性角膜炎中的角膜结构和免疫静止。这些发现为基于 HGF 的疗法在预防和治疗感染性角膜混浊方面的潜在应用提供了新的见解。
