May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Heme Oxygenase-2 Deletion Exacerbates Corneal Inflammation, Hemangiogenesis and Lymphangiogenesis
Author Affiliations & Notes
  • L. Bellner
    Pharmacology, New York Medical College, Valhalla, New York
  • E. Wandel
    Pharmacology, New York Medical College, Valhalla, New York
  • M. Vitto
    Pharmacology, New York Medical College, Valhalla, New York
  • K. A. Patil
    Pharmacology, New York Medical College, Valhalla, New York
  • M. W. Dunn
    Pharmacology, New York Medical College, Valhalla, New York
  • K. Gronert
    Pharmacology, New York Medical College, Valhalla, New York
  • M. Laniado-Schwartzman
    Pharmacology, New York Medical College, Valhalla, New York
  • Footnotes
    Commercial Relationships L. Bellner, None; E. Wandel, None; M. Vitto, None; K.A. Patil, None; M.W. Dunn, None; K. Gronert, None; M. Laniado-Schwartzman, None.
  • Footnotes
    Support NIH grants EY06513 (MLS) and EY016136 (KG).
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1699. doi:https://doi.org/
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    • Get Citation

      L. Bellner, E. Wandel, M. Vitto, K. A. Patil, M. W. Dunn, K. Gronert, M. Laniado-Schwartzman; Heme Oxygenase-2 Deletion Exacerbates Corneal Inflammation, Hemangiogenesis and Lymphangiogenesis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1699. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: Heme oxygenase (HO-1 and HO-2) represents an intrinsic cytoprotective and anti-inflammatory system based on its ability to modulate leukocyte migration and to inhibit expression of inflammatory cytokines and proteins via its products biliverdin/bilirubin and carbon monoxide (CO). We have shown that epithelial injury in HO-2 null mice leads to unresolved corneal inflammation and chronic inflammatory complications including ulceration, perforation and neovascularization (Seta et al, 2006). We now examine the consequences of HO-2 deficiency on hemangiogenesis and lymphangiogenesis in the model of suture-induced inflammatory neovascularization.

Methods:: A 8.0 silk suture was placed at the corneal apex of wild type (wt) and HO-2 null mice. Neovascularization was assessed by vital microscopy and quantified by image analysis. Hemangiogenesis and lymphangiogenesis were determined by immunofluorescence staining using anti-CD31 and anti-LYVE-1 antibodies, respectively, and quantified by image analysis. Leukocyte influx was determined by measuring myeloperoxidase activity. The expression of HO-1, HO-2 and other inflammatory proteins were determined by Western Blot analysis and real time PCR.

Results:: Corneal sutures produced a consistent inflammatory response and a time-dependent neovascularization. The response in HO-2 null mice was associated with a greater increase compared to wt in the number of leukocytes (509600±133200 vs. 148800±32910; p<0.05) and neovessels measured by vital microscopy (22.37±0.92 vs. 12.77±1.55 mm; p<0.001) 4 days after suture placement. Hemangiogenesis and lymphangiogenesis were more pronounced in HO-2 null mice compared to WT mice. The exaggerated inflammatory and neovascular response in HO-2 null mice was coupled with increased expression of inflammatory proteins, including COX-2 and CYP4B1 which produce the potent inflammatory lipid mediators, PGE2 and 12-HETrE, respectively.

Conclusions:: The demonstration that the inflammatory responses, including expression of proinflammatory proteins, inflammatory cell influx, hemangiogenesis and lymphangiogenesis are exaggerated in HO-2 knockout mice strongly supports the notion that the HO system is critical for controlling the inflammatory and neovascular response in the cornea. Hence, pharmacological amplification of this system may constitute a novel therapeutic strategy for the treatment of corneal disorders associated with neovascularization.

Keywords: inflammation • neovascularization • cornea: epithelium 
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