PEDF Reduces the Severity of Herpetic Simplex Keratitis in Mice.
PEDF Reduces the Severity of Herpetic Simplex Keratitis in Mice.
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DOI：
10.1167/iovs.18-23942
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发表时间：
2018-06
影响因子：
4.4
通讯作者：
X. Tian;Tongsong Wang;Songmei Zhang;Qian Wang;Xiaoli Hu;Cheng Ge;Lixin Xie;Qingjun Zhou
中科院分区：
文献类型：
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作者：
X. Tian;Tongsong Wang;Songmei Zhang;Qian Wang;Xiaoli Hu;Cheng Ge;Lixin Xie;Qingjun Zhou
目的探讨色素上皮衍生因子（PEDF）及其衍生肽Mer44和Mer34对小鼠单纯疱疹性角膜炎（HSK）严重程度的影响。方法C57BL/6成年小鼠眼感染1型单纯疱疹病毒（HSV-1， McKrae株），结膜下注射PEDF、Mer44或Mer34。观察急性期角膜神经退行性变、新生血管形成、敏感性、中性粒细胞、巨噬细胞、CD4+ t细胞浸润、病毒含量、VEGF、PEDF、促炎因子表达。在体外培养的猴Vero细胞中进一步评价PEDF对HSV-1复制的直接抑制作用。结果1型单纯疱疹病毒感染后，角膜PEDF表达在感染后3、7天（dpi）下降，在感染后15天（dpi）升高，在感染后45天（dpi）恢复到与正常小鼠相近的水平，并伴有角膜神经退行性变和新生血管的形成。外源性PEDF可减轻角膜神经变性和新生血管形成，改善受损角膜的敏感性。此外，PEDF可降低中性粒细胞的浸润，但不影响巨噬细胞和CD4+ t细胞的浸润，同时降低IL-1β、IL-6、TNF-α和VEGF的表达。此外，PEDF在体外和小鼠体内均能抑制HSV-1的复制。Mer44比Mer34更明显地减轻角膜神经变性，而Mer34则抑制角膜新生血管的形成。结论PEDF及其衍生肽可降低小鼠单纯疱疹性角膜炎的严重程度，是控制HSK病变的潜在治疗方法。
Purpose The purpose of this study was to explore the effects of pigment epithelium derived factor (PEDF) and PEDF-derived peptides Mer44 and Mer34 on the severity of herpetic simplex keratitis (HSK) in mice. Methods Adult C57BL/6 mice were infected ocularly with the herpes simplex virus type 1 (HSV-1, McKrae strain) and injected subconjunctivally with PEDF, Mer44, or Mer34. Corneal nerve degeneration, neovascularization, sensitivity, neutrophils, macrophages and CD4+ T-cell infiltration, virus contents, and expressions of VEGF, PEDF, and proinflammatory factors were evaluated during acute period. The direct inhibitory effect of PEDF on HSV-1 replication was further evaluated in cultured monkey Vero cells. Results Following HSV-1 infection, corneal PEDF expression decreased at 3 and 7 days postinfection (dpi) but increased at 15 dpi, and returned to the similar level of normal mice at 45 dpi, which was accompanied with the progress of corneal nerve degeneration and neovascularization. Exogenous PEDF application attenuated corneal nerve degeneration and neovascularization and improved the impaired corneal sensitivity. Moreover, PEDF attenuated the neutrophils, but not macrophage or CD4+ T-cell infiltration, with the reduced expressions of IL-1β, IL-6, TNF-α, and VEGF. In addition, PEDF inhibited the replication of HSV-1 both in vitro and in mice. Mer44 attenuated corneal nerve degeneration more significantly than Mer34, whereas Mer34 inhibited corneal neovascularization. Conclusions PEDF and its derived peptides reduce the severity of herpetic simplex keratitis in mice, representing the potential therapeutic approach to control HSK lesions.