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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.
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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.
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.
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).
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.
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