| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1From the Department of Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida; and the 2Vascular Biology Institute, University of Miami School of Medicine, Miami, Florida.
PURPOSE. Dietary fat intake has been proposed as a mechanism of sub-RPE deposit formation. It has been demonstrated recently that sub-RPE deposits develop in 16- to 18-month-old C57BL/6 mice fed a high-fat diet and exposed to blue-green light. Hyperlipidemia also develops in these mice after they consume a high-fat diet. Because hyperlipidemia also develops in young C57BL/6 mice that overexpress APO B100, the major apolipoprotein in LDL cholesterol, this research was conducted to determine whether high-fat diet and plasma hyperlipidemia correlate with formation of basal laminar deposits (BLD) in young transgenic mice.
METHODS. APO B100 and wild-type C57BL/6 2-month-old mice were fed a high-fat diet for 4.5 months. After the first month, the right eyes were exposed to seven 5-second doses of nonphototoxic levels of blue-green light (20 mJ of argon 488 nm) over 2 weeks. Three months later, transmission electron microscopy (TEM) of the retina was performed to evaluate whether sub-RPE deposits correlate with plasma cholesterol and triglyceride levels. Several eyes were stained with filipin to detect cholesterol and osmium-thiocarbohydrazide-osmium (OTO) to detect neutral lipids in Bruch’s membrane (BrM). A third group of APO B100 2-month-old mice were pretreated with vitamin E subcutaneously twice a week throughout the experiment and underwent the same light-exposure protocol.
RESULTS. Mice fed a high-fat diet had a more elevated plasma triglyceride and cholesterol level than those that consumed a regular diet. Young APO B100 mice fed a high-fat diet had blood lipid levels higher than those in young wild-type mice that consumed high-fat diets, and these two groups had higher lipid levels than animals with regular diets, as shown previously in wild-type C57BL/6 (old and young). Eyes of APO B100 mice treated with blue-green light showed a high frequency of "moderate BLD", whereas the nonexposed eyes did not. In contrast, no BLD formed in either eye of the wild-type young mice fed a high-fat diet. In individual affected mice, only a weak correlation was observed between deposit severity and plasma lipid concentration. None of the eyes in mice with sustained hyperlipidemia with or without BLD demonstrated obvious widespread neutral lipid or cholesterol deposition in BLD or BrM. However, vitamin E–treated mice showed minimal formation of BLD.
CONCLUSIONS. Although a high-fat diet is a necessary precondition for this model of BLD, the findings demonstrated a convincing direct correlation between plasma lipidemia and deposit severity. The results suggest that age, as shown in previous studies, and high-fat predispose to formation of BLD by altering hepatic and/or RPE lipid metabolism in ways more complicated than plasma hyperlipidemia alone.
This article has been cited by other articles:
|
|
 |
|
  L. Bretillon, N. Acar, M. W. Seeliger, M. Santos, M. A. Maire, P. Juaneda, L. Martine, S. Gregoire, C. Joffre, A. M. Bron, et al. ApoB100,LDLR-/- Mice Exhibit Reduced Electroretinographic Response and Cholesteryl Esters Deposits in the Retina Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1307 - 1314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Fu, D. Garland, Z. Yang, D. Shukla, A. Rajendran, E. Pearson, E. M. Stone, K. Zhang, and E. A. Pierce The R345W mutation in EFEMP1 is pathogenic and causes AMD-like deposits in mice Hum. Mol. Genet., October 15, 2007; 16(20): 2411 - 2422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tuo, C. M. Bojanowski, M. Zhou, D. Shen, R. J. Ross, K. I. Rosenberg, D. J. Cameron, C. Yin, J. A. Kowalak, Z. Zhuang, et al. Murine Ccl2/Cx3cr1 Deficiency Results in Retinal Lesions Mimicking Human Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., August 1, 2007; 48(8): 3827 - 3836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. L. Tan, P. Mitchell, A. Kifley, V. Flood, W. Smith, and J. J. Wang Smoking and the Long-term Incidence of Age-Related Macular Degeneration: The Blue Mountains Eye Study Arch Ophthalmol, August 1, 2007; 125(8): 1089 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Marin-Castano, G. E. Striker, O. Alcazar, P. Catanuto, D. G. Espinosa-Heidmann, and S. W. Cousins Repetitive Nonlethal Oxidant Injury to Retinal Pigment Epithelium Decreased Extracellular Matrix Turnover In Vitro and Induced Sub-RPE Deposits In Vivo. Invest. Ophthalmol. Vis. Sci., September 1, 2006; 47(9): 4098 - 4112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N Dashti, G McGwin, C Owsley, and C A Curcio Plasma apolipoproteins and risk for age related maculopathy Br. J. Ophthalmol., August 1, 2006; 90(8): 1028 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-M. Li, M. E. Clark, M. F. Chimento, and C. A. Curcio Apolipoprotein localization in isolated drusen and retinal apolipoprotein gene expression. Invest. Ophthalmol. Vis. Sci., July 1, 2006; 47(7): 3119 - 3128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Espinosa-Heidmann, I. J. Suner, P. Catanuto, E. P. Hernandez, M. E. Marin-Castano, and S. W. Cousins Cigarette Smoke-Related Oxidants and the Development of Sub-RPE Deposits in an Experimental Animal Model of Dry AMD Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 729 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Marneros and B. R. Olsen Physiological role of collagen XVIII and endostatin FASEB J, May 1, 2005; 19(7): 716 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Fernandez-Robredo, D. Moya, J. A. Rodriguez, and A. Garcia-Layana Vitamins C and E Reduce Retinal Oxidative Stress and Nitric Oxide Metabolites and Prevent Ultrastructural Alterations in Porcine Hypercholesterolemia Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1140 - 1146. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
