Amino-Retinoid Compounds in the Human Retinal Pigment Epithelium

Abstract

For many years, blue light damage associated with retinal pigment epithelial (RPE) cell lipofuscin (LF) has been implicated in the cause of age-related macular degeneration (AMD) (Young, 1988; Winkler et al., 1999; Bressler et al., 2000) and other retinal degenerative diseases, such as Stargardt’s disease, (Lopez et al., 1990; Birnbach et al., 1994), Best’s macular dystrophy (Weingeist et al., 1982) and cone-rod dystrophy (Rabb et al., 1986). A2E and isomers, pyridinium bis-retinoid compounds and only major blue-light absorbing fluorophores isolated from human LF, (Eldred and Katz, 1988; Eldred and Lasky, 1993; Sakai et al., 1996; Parish et al., 1998;) account for a small fraction of the composition of LF. Proteins account for 30–70% (Schutt et al., 2002; Haralampus-Grynaviski et al., 2003). The percentage of A2E oxidation products, retinol and retinyl palmitate has not been quantified, yet these compounds, too, make up only a fraction of the composition of LF. Evidence for A2E and especially A2E photo-oxidation products’ involvement in AMD is strong (Sparrow et al., 1999; Sparrow et al., 2000; Sparrow and Cai, 2001; Ben-Shabat et al., 2002a; Finnemann et al., 2002; Sparrow et al., 2002; Sparrow et al., 2003); however, their involvement does not rule out the possibility of AMD’s etiology being multifactorial. There are many compounds in LF that have not been characterized, some of which may also play a role in the pathogenesis of AMD and other retinal degenerative diseases.