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Recurrent Herpetic Stromal Keratitis in Mice, a Model for Studying Human HSK
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PEDF Reduces the Severity of Herpetic Simplex Keratitis in Mice

Xiao Tian1, Tongsong Wang1, Songmei Zhang1

  • 1State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China.

Investigative Ophthalmology & Visual Science
|July 20, 2018
PubMed
Abstract

Insights

Pigment epithelium derived factor (PEDF) and its peptides Mer44 and Mer34 effectively reduce herpetic simplex keratitis (HSK) severity in mice. These findings suggest a promising therapeutic strategy for managing HSK lesions.

Area of Science:

  • Ophthalmology
  • Virology
  • Immunology

Background:

  • Herpetic simplex keratitis (HSK) is a viral infection of the cornea caused by herpes simplex virus type 1 (HSV-1).
  • Corneal nerve damage, inflammation, and neovascularization are key pathological features of HSK.
  • Current treatments for HSK have limitations, necessitating the exploration of novel therapeutic agents.

Purpose of the Study:

  • To investigate the therapeutic potential of pigment epithelium derived factor (PEDF) and its derived peptides, Mer44 and Mer34, in a mouse model of HSK.
  • To evaluate the effects of PEDF and its peptides on viral replication, corneal nerve integrity, inflammation, and neovascularization during HSK.

Main Methods:

  • Adult C57BL/6 mice were infected with HSV-1 (McKrae strain) and treated with subconjunctival injections of PEDF, Mer44, or Mer34.
  • Evaluated parameters included corneal nerve degeneration, neovascularization, sensitivity, immune cell infiltration (neutrophils, macrophages, CD4+ T-cells), viral load, and expression of VEGF and inflammatory cytokines.
  • In vitro antiviral activity of PEDF against HSV-1 was assessed in cultured monkey Vero cells.

Main Results:

  • Exogenous PEDF application significantly attenuated corneal nerve degeneration, neovascularization, and improved corneal sensitivity in HSV-1 infected mice.
  • PEDF reduced neutrophil infiltration and suppressed the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and VEGF.
  • Mer44 demonstrated superior efficacy in reducing corneal nerve degeneration, while Mer34 was more effective in inhibiting corneal neovascularization.
  • PEDF exhibited direct antiviral activity, inhibiting HSV-1 replication both in vitro and in vivo.

Conclusions:

  • PEDF and its peptides, Mer44 and Mer34, demonstrate significant therapeutic benefits in reducing the severity of herpetic simplex keratitis in a mouse model.
  • These findings highlight PEDF and its derivatives as potential novel therapeutic agents for controlling HSK lesions and improving corneal health.

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