Bhattacharjee Partha S, Neumann Donna M, Foster Timothy P, Clement Christian, Singh Gyanendra, Thompson Hilary W, Kaufman Herbert E, Hill James M
Departments of Ophthalmology, School of Public Health, LouisianaState University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4263-8. doi: 10.1167/iovs.08-2077. Epub 2008 May 30.
To evaluate efficacy of the small apolipoprotein E (apoE) mimetic dimer peptide (apoEdp) in the treatment of herpetic stromal keratitis in a mouse ocular model and determine its therapeutic effects against HSV-1-induced inflammatory cytokines.
Female C57Bl/6 mice were corneally infected with HSV-1 strain KOS-GFP; topical treatment was initiated 24 hours after infection and continued for 10 consecutive days. Treatment groups were 1% apoEdp, 1% trifluorothymidine (TFT), and phosphate-buffered saline (PBS). The incidence and severity of stromal keratitis were monitored by slit lamp examination in a masked fashion. Infectious HSV-1 titer in eye swabs and alteration in inflammatory cytokines were determined in the early postinfection period by real-time RT-PCR.
One percent apoEdp treatment, which significantly reduced the incidence and severity of HSK, was equal to the effect of 1% TFT; both groups had significantly lower incidence and severity than the placebo treatment group. The in vivo mouse ocular model results of apoEdp therapy correlated with accelerated clearance of virus from eye swabs. Topical 1% apoEdp treatment in mice significantly downregulated gene expression of mouse proinflammatory cytokines.
These results suggest that topical treatment with apoE peptide has efficacy against HSK through anti-HSV-1 and anti-inflammatory activities.
在小鼠眼部模型中评估小载脂蛋白E（apoE）模拟二聚体肽（apoEdp）治疗疱疹性基质性角膜炎的疗效，并确定其对单纯疱疹病毒1型（HSV-1）诱导的炎性细胞因子的治疗效果。
雌性C57Bl/6小鼠角膜感染HSV-1毒株KOS-GFP；感染后24小时开始局部治疗，持续10天。治疗组分别为1% apoEdp、1%三氟胸腺嘧啶核苷（TFT）和磷酸盐缓冲盐水（PBS）。通过裂隙灯检查以盲法监测基质性角膜炎的发病率和严重程度。在感染后早期，通过实时逆转录聚合酶链反应（RT-PCR）测定眼拭子中感染性HSV-1滴度和炎性细胞因子的变化。
1% apoEdp治疗显著降低了疱疹性基质性角膜炎的发病率和严重程度，其效果与1% TFT相当；两组的发病率和严重程度均显著低于安慰剂治疗组。apoEdp治疗的体内小鼠眼部模型结果与眼拭子中病毒清除加速相关。小鼠局部应用1% apoEdp治疗可显著下调小鼠促炎细胞因子的基因表达。
这些结果表明，apoE肽局部治疗通过抗HSV-1和抗炎活性对疱疹性基质性角膜炎有效。
