PURPOSE: Oxidative injury to the retinal pigment epithelium (RPE) has been proposed to be an important injury stimulus relevant to the accumulation of subretinal deposits in age-related macular degeneration (AMD). Cigarette smoking is a major risk factor for AMD, and cigarette smoke-related tar contains high concentrations of a potent oxidant, hydroquinone (HQ). This study was an investigation of the effects of cigarette smoke (CS) and HQ in the development of sub-RPE deposits in an experimental mouse model. METHODS: Sixteen-month-old C57BL/6 female mice were fed a high-fat diet (HFD) for 4.5 months. Mice were divided into two major experimental groups, one to examine the effects of cigarette smoke and one to study the effects of a defined cigarette smoke component such as HQ. In the first group, mice eyes were exposed to blue-green light (positive controls) or to whole cigarette smoke. A third group with no intervention served as the negative control. In the second experimental group, animals received a purified diet with HQ (0.8%) with low or high fat content for 4.5 months. Mice in both groups were euthanatized at 4.5 months and eyes processed for transmission electron microscopy. RESULTS: As previously demonstrated by our laboratory and others, most mice fed an HFD without other oxidant exposure demonstrated normal morphology or, in a few cases, small nodular basal laminar deposits. Eyes of mice exposed to whole cigarette smoke or to HQ in the food demonstrated a variable degree of basal laminar deposits and diffusely thickened Bruch's membrane. The choriocapillaris endothelium was variably hypertrophic. CONCLUSIONS: Exposure to cigarette smoke or the smoke-related redox molecule, HQ, results in the formation of sub-RPE deposits, thickening of Bruch's membrane, and accumulation of deposits within Bruch's membrane. Smoke-related oxidants may be another oxidative injury stimulus to the choriocapillaris and RPE, and may explain the association between cigarette smoking and early AMD.
PURPOSE: Oxidative injury to the retinal pigment epithelium (RPE) has been proposed to be an important injury stimulus relevant to the accumulation of subretinal deposits in age-related macular degeneration (AMD). Cigarette smoking is a major risk factor for AMD, and cigarette smoke-related tar contains high concentrations of a potent oxidant, hydroquinone (HQ). This study was an investigation of the effects of cigarette smoke (CS) and HQ in the development of sub-RPE deposits in an experimental mouse model. METHODS: Sixteen-month-old C57BL/6 female mice were fed a high-fat diet (HFD) for 4.5 months. Mice were divided into two major experimental groups, one to examine the effects of cigarette smoke and one to study the effects of a defined cigarette smoke component such as HQ. In the first group, mice eyes were exposed to blue-green light (positive controls) or to whole cigarette smoke. A third group with no intervention served as the negative control. In the second experimental group, animals received a purified diet with HQ (0.8%) with low or high fat content for 4.5 months. Mice in both groups were euthanatized at 4.5 months and eyes processed for transmission electron microscopy. RESULTS: As previously demonstrated by our laboratory and others, most mice fed an HFD without other oxidant exposure demonstrated normal morphology or, in a few cases, small nodular basal laminar deposits. Eyes of mice exposed to whole cigarette smoke or to HQ in the food demonstrated a variable degree of basal laminar deposits and diffusely thickened Bruch's membrane. The choriocapillaris endothelium was variably hypertrophic. CONCLUSIONS: Exposure to cigarette smoke or the smoke-related redox molecule, HQ, results in the formation of sub-RPE deposits, thickening of Bruch's membrane, and accumulation of deposits within Bruch's membrane. Smoke-related oxidants may be another oxidative injury stimulus to the choriocapillaris and RPE, and may explain the association between cigarette smoking and early AMD.
Authors: Elizabeth Monaghan-Benson; John Hartmann; Aleksandr E Vendrov; Steve Budd; Grace Byfield; Augustus Parker; Faisal Ahmad; Wei Huang; Marschall Runge; Keith Burridge; Nageswara Madamanchi; M Elizabeth Hartnett Journal: Am J Pathol Date: 2010-08-27 Impact factor: 4.307
Authors: Oscar Alcazar; Adam M Hawkridge; Timothy S Collier; Scott W Cousins; Sanjoy K Bhattacharya; David C Muddiman; Maria E Marin-Castano Journal: Mol Cell Proteomics Date: 2009-06-29 Impact factor: 5.911
Authors: Sheldon Rowan; Shuhong Jiang; Tal Korem; Jedrzej Szymanski; Min-Lee Chang; Jason Szelog; Christa Cassalman; Kalavathi Dasuri; Christina McGuire; Ryoji Nagai; Xue-Liang Du; Michael Brownlee; Naila Rabbani; Paul J Thornalley; James D Baleja; Amy A Deik; Kerry A Pierce; Justin M Scott; Clary B Clish; Donald E Smith; Adina Weinberger; Tali Avnit-Sagi; Maya Lotan-Pompan; Eran Segal; Allen Taylor Journal: Proc Natl Acad Sci U S A Date: 2017-05-15 Impact factor: 11.205
Authors: Katsuji Kiuchi; Masato Matsuoka; Jenny C Wu; Raquel Lima e Silva; Muralitharan Kengatharan; Mary Verghese; Shinji Ueno; Katsutoshi Yokoi; Naw Htee Khu; John P Cooke; Peter A Campochiaro Journal: Invest Ophthalmol Vis Sci Date: 2008-04 Impact factor: 4.799