May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Effects of ApoE Deficiency, Aging and High Fat Diet on Laser-Induced Choroidal Neovascularization and Bruch's Membrane-RPE Interface Morphology
Author Affiliations & Notes
  • D. Skondra
    Angiogenesis and Laser Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • H. She
    Angiogenesis and Laser Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • H. J. Zambarakji
    Angiogenesis and Laser Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • E. Connolly
    Angiogenesis and Laser Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • N. Michaud
    Angiogenesis and Laser Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • P. Chan
    Angiogenesis and Laser Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • I. K. Kim
    Angiogenesis and Laser Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • E. S. Gragoudas
    Angiogenesis and Laser Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • J. W. Miller
    Angiogenesis and Laser Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • A. Hafezi-Moghadam
    Angiogenesis and Laser Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships D. Skondra, None; H. She, None; H.J. Zambarakji, None; E. Connolly, None; N. Michaud, None; P. Chan, None; I.K. Kim, None; E.S. Gragoudas, None; J.W. Miller, 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, 1768. doi:https://doi.org/
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      D. Skondra, H. She, H. J. Zambarakji, E. Connolly, N. Michaud, P. Chan, I. K. Kim, E. S. Gragoudas, J. W. Miller, A. Hafezi-Moghadam; Effects of ApoE Deficiency, Aging and High Fat Diet on Laser-Induced Choroidal Neovascularization and Bruch's Membrane-RPE Interface Morphology. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1768. doi: https://doi.org/.

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

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Abstract

Purpose:: To investigate the role of apolipoprotein E (apoE), high fat diet and aging on the development of choroidal neovascularization (CNV) and the morphology of the Bruch's membrane-RPE interface.

Methods:: Young (9-12 weeks old) and old (19 months old) age-matched apoE deficient (apoE-/-) and wild type (WT) mice on C57BL/6J background were fed normal (ND) or Western Diet (WD) for 6 weeks prior to laser injury. Laser-induced choroidal neovascular membranes were assessed 2 weeks after laser injury for vascular leakage using fluorescein angiography (FA) and for lesion size in FITC-dextran perfused choroidal flatmounts. Bruch's membrane and RPE morphology were examined using transmission electron microscopy.

Results:: Young apoE-/- mice on ND showed 34% more CNV lesions with clinically significant leakage compared to young WT mice on ND (P<0.01), while CNV size was not statistically different between the two groups (P=0.9). Young WT mice on WD showed a 24% increase in the number of highly leaky lesions (P=0.01) and a 173% increase in CNV size (P=0.04) compared with young WT mice on ND. Young apoE-/- mice on WD showed a 275% increase in CNV size (P=0.01) compared to young apoE-/- mice on ND, however CNV vascular leakage was not statistically different between the 2 groups (P=0.4). Old WT and apoE-/- mice on ND did not show differences in leaky lesions or CNV size (P=0.6 and 0.3, respectively). Old WT mice on ND showed a significant 126% increase in CNV size compared to young WT mice on ND (P=0.02) and 55% more leaky lesions but the difference did not reach statistical significance (P=0.1). Old apoE-/- mice on ND showed a 26% increase in clinically significant leakage (P<0.01) and a 44% increase in CNV size (P=0.1) compared to young apoE-/- mice on ND. Old WT mice on ND developed sporadic sub-RPE deposits, while old apoE-/- mice on ND developed larger and more extensive deposits and disorganization of the basal infoldings of RPE cells. WD for 9 months increased sub-RPE deposit formation in aged WT and apoE-/- mice.

Conclusions:: These data suggest that apoE deficiency, high fat diet and aging may increase CNV vascular leakage, CNV size and development of sub-RPE deposits.

Keywords: age-related macular degeneration • aging • lipids 
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