TY - JOUR
T1 - Cholesterol-enriched diet causes age-related macular degeneration-like pathology in rabbit retina
AU - Dasari, Bhanu
AU - Prasanthi, Jaya Rp
AU - Marwarha, Gurdeep
AU - Singh, Brij B.
AU - Ghribi, Othman
N1 - Funding Information:
Supported by a grant from NIEHS/NIH to OG (R01ES014826). The authors thank Dr. David Russell (University of Texas South Western Medical Center) for measurements of oxysterols with mass spectrometry. The authors also thank Dr. Byron Grove and Sarah Rolling (Department of Anatomy and Cell Biology, School of Medicine & Health Sciences, University of North Dakota) for their technical assistance in confocal microscopy.
PY - 2011
Y1 - 2011
N2 - Background: Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several pathological hallmarks including β-amyloid (Aβ) accumulation, oxidative stress, and apoptotic cell death. The causes of AD and AMD are likely multi-factorial with several factors such as diet, environment, and genetic susceptibility participating in the pathogenesis of these diseases. Epidemiological studies correlated high plasma cholesterol levels with high incidence of AD, and feeding rabbits with a diet rich in cholesterol has been shown to induce AD-like pathology in rabbit brain. High intake of cholesterol and saturated fat were also long been suspected to increase the risk for AMD. However, the extent to which cholesterol-enriched diet may also cause AMD-like features in rabbit retinas is not well known. Methods. Male New Zealand white rabbits were fed normal chow or a 2% cholesterol-enriched diet for 12 weeks. At necropsy, animals were perfused with Dulbecco's phosphate-buffered saline and the eyes were promptly removed. One eye of each animal was used for immunohistochemistry and retina dissected from the other eye was used for Western blot, ELISA assays, spectrophotometry and mass spectrometry analyses. Results: Increased levels of Aβ, decreased levels of the anti-apoptotic protein Bcl-2, increased levels of the pro-apoptotic Bax and gadd153 proteins, emergence of TUNEL-positive cells, and increased generation of reactive oxygen species were found in retinas from cholesterol-fed compared to normal chow-fed rabbits. Additionally, astrogliosis, drusen-like debris and cholesterol accumulations in retinas from cholesterol-fed rabbits were observed. As several lines of evidence suggest that oxidized cholesterol metabolites (oxysterols) may be the link by which cholesterol contributes to the pathogenesis of AMD, we determined levels of oxysterols and found a dramatic increase in levels of oxysterols in retinas from cholesterol-fed rabbits. Conclusions: Our results suggest that cholesterol-enriched diets cause retinal degeneration that is relevant to AMD. Furthermore, our data suggests high cholesterol levels and subsequent increase in the cholesterol metabolites as potential culprits to AMD.
AB - Background: Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several pathological hallmarks including β-amyloid (Aβ) accumulation, oxidative stress, and apoptotic cell death. The causes of AD and AMD are likely multi-factorial with several factors such as diet, environment, and genetic susceptibility participating in the pathogenesis of these diseases. Epidemiological studies correlated high plasma cholesterol levels with high incidence of AD, and feeding rabbits with a diet rich in cholesterol has been shown to induce AD-like pathology in rabbit brain. High intake of cholesterol and saturated fat were also long been suspected to increase the risk for AMD. However, the extent to which cholesterol-enriched diet may also cause AMD-like features in rabbit retinas is not well known. Methods. Male New Zealand white rabbits were fed normal chow or a 2% cholesterol-enriched diet for 12 weeks. At necropsy, animals were perfused with Dulbecco's phosphate-buffered saline and the eyes were promptly removed. One eye of each animal was used for immunohistochemistry and retina dissected from the other eye was used for Western blot, ELISA assays, spectrophotometry and mass spectrometry analyses. Results: Increased levels of Aβ, decreased levels of the anti-apoptotic protein Bcl-2, increased levels of the pro-apoptotic Bax and gadd153 proteins, emergence of TUNEL-positive cells, and increased generation of reactive oxygen species were found in retinas from cholesterol-fed compared to normal chow-fed rabbits. Additionally, astrogliosis, drusen-like debris and cholesterol accumulations in retinas from cholesterol-fed rabbits were observed. As several lines of evidence suggest that oxidized cholesterol metabolites (oxysterols) may be the link by which cholesterol contributes to the pathogenesis of AMD, we determined levels of oxysterols and found a dramatic increase in levels of oxysterols in retinas from cholesterol-fed rabbits. Conclusions: Our results suggest that cholesterol-enriched diets cause retinal degeneration that is relevant to AMD. Furthermore, our data suggests high cholesterol levels and subsequent increase in the cholesterol metabolites as potential culprits to AMD.
UR - http://www.scopus.com/inward/record.url?scp=80051795545&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80051795545&partnerID=8YFLogxK
U2 - 10.1186/1471-2415-11-22
DO - 10.1186/1471-2415-11-22
M3 - Article
C2 - 21851605
AN - SCOPUS:80051795545
SN - 1471-2415
VL - 11
JO - BMC Ophthalmology
JF - BMC Ophthalmology
IS - 1
M1 - 22
ER -