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
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
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:
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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.

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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 
© 2007, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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