Alcohol linked to enhanced angiogenesis in rat model of choroidal neovascularization.
One of the pathologic complications of exudative (i.e. wet-type) age-related macular degeneration (AMD) is choroidal neovascularization (CNV). The aim of this study was to investigate whether chronic and heavy alcohol consumption influenced the development of CNV in a rat model. The oxidative metabolism of alcohol is minimal or absent in the eye, so that ethanol is metabolized via a nonoxidative pathway to form fatty acid ethyl esters (FAEE). Fatty acid ethyl ester synthase (FAEES) was purified from the choroid of Brown Norway (BN) rats. The purified protein was 60 kDa in size and the antibody raised against this protein showed a single band on western blot. BN rats on a regular diet were fed alcohol for 10 weeks. Control rats were fed water with a regular diet and pair-fed control rats were fed regular diet, water and glucose. We found that FAEES activity was increased 4.0-fold in the choroid of alcohol-treated rats compared with controls. The amount of ethyl esters produced in the choroid of 10 week alcohol-fed rats was 7.4-fold more than rats fed alcohol for 1 week. The increased accumulation of ethyl esters was associated with a 3.0-fold increased expression of cyclin E and cyclin E/CDK2; however, the level of the cyclin kinase inhibitor, p27Kip, did not change. The increased accumulation of ethyl esters was also associated with 3.0-fold decreased expression of APN in the choroid. We also found that the size of CNV increased by 28% in alcohol-fed rats. Thus, our study showed that chronic, heavy alcohol intake was associated with both an increased accumulation of ethyl esters in the choroid and an exacerbation of the CNV induced by laser treatment. These results may provide insight into the link between heavy alcohol consumption and exudative AMD.
Bora
Puran S
PS
Department of Ophthalmology and Visual Science, Kentucky Lions Eye Center, University of Louisville, KY, USA. pbora@uams.edu
Kaliappan
Sankaranarayanan
S
Xu
Qin
Q
Kumar
Shalesh
S
Wang
Yali
Y
Kaplan
Henry J
HJ
Bora
Nalini S
NS
D000217:Acyltransferases / Q000302:isolation & purification / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000428:Alcohol Drinking / Q000009:adverse effects / Q000473:pathology; D000818:Animals; D020256:Choroidal Neovascularization / Q000503:physiopathology*; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D004952:Esters / Q000737:chemistry / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism*; D005123:Eye / Q000033:anatomy & histology; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051381:Rats
D052242:Adiponectin; D019927:Cyclin E; D004952:Esters; D005227:Fatty Acids; D000431:Ethanol; D000217:Acyltransferases; D051357:Cyclin-Dependent Kinase 2; C043403:fatty acyl ethyl ester synthase