June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Loss of HSV-1 induced VEGF-A during acute infection impairs the lymphangiogenic response during later stages of disease
Author Affiliations & Notes
  • Katie Hudson
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • Min Zheng
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • Daniel Carr
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
    Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • Footnotes
    Commercial Relationships Katie Hudson, None; Min Zheng, None; Daniel Carr, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1729. doi:
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      Katie Hudson, Min Zheng, Daniel Carr; Loss of HSV-1 induced VEGF-A during acute infection impairs the lymphangiogenic response during later stages of disease. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1729.

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Abstract

Purpose: To characterize the impact of HSV-1 induced VEGF-A on lymphangiogenesis in the cornea during the development of herpetic stromal keratitis (HSK) and viral latency.

Methods: VEGF-A floxed C57BL/6 mice were infected with 200 pfu/cornea of HSV-1, either parental (SC16) or Cre-expressing (SC16 ICP0-Cre). At various time points post-infection (PI) mice were exsanguinated and the corneas were stained for blood (CD31+) and lymphatic (LYVE-1+) vessels. Viral load within the corneas was evaluated by plaque assay. Corneal leukocyte recruitment was determined by flow cytometry. Relative expression of pro-lymphangiogenic growth factors was determined via real-time RT-PCR.

Results: VEGF-A floxed mice infected with Cre-expressing HSV-1 had reduced T cell recruitment to the cornea at days 7 and 14 PI compared to floxed mice infected with the parental virus. Lymphatic vessel development into the cornea proper was also reduced at days 14 and 30 PI in the Cre-expressing HSV-1 infected group. Blood vessel development into the central cornea was similar for both groups. VEGF-A and VEGF-C expression was reduced at day 7 PI in ICP0-Cre infected floxed mice compared to the parental strain.

Conclusions: Preliminary results indicate loss of HSV-1 induced VEGF-A during acute infection significantly impairs the lymphangiogenic but not hemangiogenic response during the development of HSK and the establishment of viral latency. Reduced lymphatic vessel development may be due to a skewed pattern of leukocyte recruitment and subsequent expression of pro-lymphangiogenic factors.

Keywords: 480 cornea: basic science • 545 herpes simplex virus • 609 neovascularization  
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