May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Enhanced Age-Related Corneal Angiogenesis in Apolipoprotein E-Deficient Mice
Author Affiliations & Notes
  • S. Nakao
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • K. Noda
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • L. Almulki
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • T. Hisatomi
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • K. L. Thomas
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • J. W. Miller
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • E. S. Gragoudas
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • A. Hafezi-Moghadam
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships S. Nakao, None; K. Noda, None; L. Almulki, None; T. Hisatomi, None; K.L. Thomas, None; J.W. Miller, None; E.S. Gragoudas, None; A. Hafezi-Moghadam, None.
  • Footnotes
    Support NEI core grant EY14104, NIH grant AI050775 to A.H.M., Massachusetts Lions Foundation, and Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1726. doi:https://doi.org/
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    • Get Citation

      S. Nakao, K. Noda, L. Almulki, T. Hisatomi, K. L. Thomas, J. W. Miller, E. S. Gragoudas, A. Hafezi-Moghadam; Enhanced Age-Related Corneal Angiogenesis in Apolipoprotein E-Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1726. doi: https://doi.org/.

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

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Abstract

Purpose:: Age is the most important risk factor for age-related macular degeneration (AMD). Furthermore, epidemiologic and experimental studies have revealed an association between apolipoprotein E (apoE) and AMD. However, the mechanisms underlying how apoE contributes to the pathogenesis of AMD are unknown. Inflammatory and angiogenic factors such as fibroblast growth factor-2 (FGF-2) play an important role in AMD. Here, we investigate the role of apoE in FGF-2-induced corneal angiogenesis during aging.

Methods:: Young (6-12 weeks old) C57BL/6 wild type (WT) and apoE-/- mice or aged (8 months old) WT and apoE-/- mice were used for experiments. To induce neovascularization, FGF-2 pellets (100ng) were implanted in the corneas using the established micro-pocket assay. Corneal neovascularization was quantified on day 6 post FGF-2 implantation. To do so, in vivo CD31-staining was performed and corneal flat mounts were generated. The amount of neovascularization was determined from digital micrographs obtained by epifluorescence microscopy.

Results:: In young apoE-/- mice, FGF-2 induced corneal angiogenesis at levels similar to those of young WT mice (WT: 1.7±0.7mm2, apoE-/-: 1.6±0.3mm2, n=5 and 6, p=0.8). In contrast, FGF-2-induced angiogenesis in aged apoE-/- mice was significantly enhanced, compared with that of age-matched WT mice (WT: 1.8±0.6mm2, apoE-/-: 2.6±0.8mm2, n=9 and 11, p=0.01) or when compared to young apoE-/- mice (p=0.02). Interestingly, aged WT mice did not show a higher amount of FGF-2-induced angiogenesis compared to young WT mice (p=0.8).

Conclusions:: Age or apoE-deficiency alone does not affect the angiogenic response to FGF-2. However, age and apoE-deficiency together significantly increase FGF-2-induced neovascularization. Since both age and apoE are important risk factors for AMD, our findings may thus have implications for angiogenic and age-related diseases, such as AMD.

Keywords: aging • neovascularization 
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