A2E, A Fluorophore of RPE Lipofuscin, Can Destabilize Membrane

Abstract

Studies of Stargardt disease suggest a role for RPE lipofuscin in the RPE cell atrophy that characterizes macular degeneration. The best known constituent of RPE lipofuscin is the pyridinium bisretinoid, A2E (Eldred and Lasky, 1993; Parish et al., 1998). Amongst the properties of A2E that may be damaging to the RPE cell is its ability to destabilize cell membranes (Sparrow et al., 1999). A hydrophilic head group combined with a pair of hydrophobic side-arms are the structural correlates of this behavior. This amphiphilic structure accounts for the tendency of A2E to aggregate (Sakai et al., 1996; De and Sakmar, 2002), a behavior first recognized in deuterated chloroform (CDCl₃), the broadening of the ¹H NMR signal indicating that the protonated pyridinium moieties of A2E were closely packed within the interior of micelles while the hydrophobic chains contacted the solvent. Further evidence of the detergent-like behaviour of A2E has been revealed in experiments demonstrating the ability of A2E to induce concentration-dependent membrane leakage (Sparrow et al., 1999). In studies employing unilamellar vesicles, it has also been shown that A2E, at critical micellar concentrations, can solubilize membranes (De and Sakmar, 2002).