A mechanistic study of the photooxidation of A2E, a component of human retinal lipofuscin.
A major constituent of human retinal lipofuscin is A2E (2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hydroxyethyl)-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-hexatrienyl]-pyridinium). Light transmitted by the lens is absorbed by A2E and the processes initiated by this absorption has been implicated in several maculopothies. The purpose of this study was to evaluate the dominant photochemical mechanisms involved in these reactions, whether through free radical or singlet oxygen intermediacy. The photodestruction of A2E occurs faster in water vs. chloroform and hydrogenated vs. perdeuterated methanol. Both results suggest a free radical mechanism. Product distributions indicate sequential oxygen addition rather than the addition of two oxygen atoms which would be expected if singlet oxygen was an intermediate. Finally, EPR trapping studies lead to the detection of superoxide as the primary intermediate in the photochemical reactions. It is concluded that if singlet oxygen is involved in these photochemical processes it is of minor importance.
Gaillard
E R
ER
Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb 60115, USA. gaillard@niu.edu
Avalle
L B
LB
Keller
L M M
LM
Wang
Z
Z
Reszka
K J
KJ
Dillon
J P
JP
D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010777:Photochemistry; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D011726:Pyridinium Compounds / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
C112040:A2-E (N-retinylidene-N-retinylethanolamine); D005609:Free Radicals; D008062:Lipofuscin; D011726:Pyridinium Compounds; D012176:Retinoids; D013481:Superoxides; D010100:Oxygen