The photochemical oxidation of A2E results in the formation of a 5,8,5',8'-bis-furanoid oxide.
With age and certain diseases, the retinal pigment epithelium (RPE) accumulates a complex mixture of fluorophores generally called lipofuscin. This mixture has been implicated in those diseases via several possible mechanisms including photochemically mediated damage and detergent effects. Recently, a component of that mixture has been identified, a bis-retinoid pyridinium compound called A2E. Furthermore, the photolysis of this compound has been shown to lead to a series of photooxidation products each differing by 16 amu; with the addition of up to a total of nine oxygen atoms to A2E. It has been suggested that these products consist of a series of epoxides forming along the acyclic side chains. The present study reinvestigates this hypothesis and demonstrates that the bis-oxygenated product is in fact a relatively stable 5-8 5'-8'-bis-furanoid oxide. This is in agreement with the oxidation products observed for a homologue of A2E, beta-carotene. In addition, it was found that the bis-oxygenated photoproduct of A2E contained a mixture of symmetrical and unsymmetrical oxidized products where the second oxygen was present in the cyclohexenyl ring structure in the unsymmetrical product. Most importantly, both of these oxidation products of A2E were detected in lipofuscin extracts from human RPE cells, suggesting that these processes occur in vivo.
Dillon
J
J
Department of Ophthalmology, Columbia University, New York, NY 100322, USA.
Wang
Z
Z
Avalle
L B
LB
Gaillard
E R
ER
D005663:Furans / Q000737:chemistry*; D006801:Humans; D008062:Lipofuscin / Q000737:chemistry; D010083:Oxidants, Photochemical / Q000737:chemistry*; D010084:Oxidation-Reduction; D010782:Photolysis; D010857:Pigment Epithelium of Eye / Q000737:chemistry*; D011726:Pyridinium Compounds / Q000737:chemistry*; D012176:Retinoids / Q000737:chemistry*; D019207:beta Carotene / Q000737:chemistry
C493101:5,8,5',8'-bis-furanoid oxide; C112040:A2-E (N-retinylidene-N-retinylethanolamine); D005663:Furans; D008062:Lipofuscin; D010083:Oxidants, Photochemical; D011726:Pyridinium Compounds; D012176:Retinoids; D019207:beta Carotene