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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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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
These data suggest that apoE deficiency, high fat diet and aging may increase CNV vascular leakage, CNV size and development of sub-RPE deposits.
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