smokers than non-smokers (Bernhard et al. 2006). Cadmium accumulates preferentially in the RPE and choroid (Wills et al. 2008) and may contribute to the development of AMD through an increase in reactive oxygen species. Cadmium exposure reduces viability and membrane integrity of cultured RPE cells and this damage was likely oxidative (Wills et al. 2008). Interestingly, cadmium has been found at increased concentrations in the urine of smokers and non-smokers with AMD supporting a role for cadmium in the pathogenesis of AMD (Eric et al. 2007).

50.4 Cigarette Smoke Depletion of Antioxidant Protection

50.4.1 Systemic Antioxidant Mechanisms

Several systems exist to protect against oxidant-mediated cellular damage. Diet derived antioxidant vitamins B, C and E provide protection by reacting with radicals terminating oxidation cascades. Cigarette smoke depletes plasma concentrations of vitamin C, E and carotenoids (Chow et al. 1986; Alberg 2002; Panda et al. 1999; Bruno and Traber 2006) and supplementation of antioxidants inhibits cigarette smoke induced oxidative damage in vivo (Panda et al. 2000).Acute cigarette smoke exposure also reduces the levels of endogenous circulating anti-oxidant molecules. Glutatione, cysteine, methylumbellifere glucuronide and ferrodxidase are all reduced in serum after smoke exposure (Moriarty et al. 2003; Van der Vaart et al. 2004). Enzymes that degrade reactive molecules and generate endogenous antioxidants such as superoxide dismutase (SOD), catalase and glutathione peroxidase are also crucial in cellular defense against oxidative damage. Distuption of superoxide dismutase in mice results in drusen-like deposits in the eye, and SOD knock-out animals have been used as a model of dry-AMD (Edwards and Malek 2007).

50.4.2 Local Ocular Antioxidants

Carotenoids are present in a large concentration in the macula giving it a yellowish appearance and providing protection from oxidative damage (Loane et al. 2008). Reduced levels of macular pigments have been associated with AMD, due to the loss of this antioxidant protective capacity (O’Connell et al. 2006). Supplementary therapy with dietary macular pigments may offset this damage and reduce disease progression in macular degeneration. Cigarette smoking has been shown to reduce macular pigment (Hammond et al. 1996) and, by compromising local antioxidant protection, may promote AMD.