Photochemistry of all-trans-retinal and all-trans-retinal derivatives related to human retinal lipofuscin.

摘要

Macular dystrophies such as age-related macular degeneration (ARMD) are characterized by the accumulation of a mixture of components called lipofuscin. The accumulation of lipofuscin has been correlated with exposure to ambient radiation and loss of photoreceptors. The main fluorescent component of lipofuscin is a compound called A2-E, which is a derivative of all- trans-retinal and ethanolamine. The exact details of the mechanism of formation of lipofuscin are not fully understood, including the role that ambient radiation plays in the process, though photooxidative mechanisms are thought to be involved. The bulk of this work consists of investigations of the photooxidative properties of all-trans-retinal and the photophysical and photochemical properties of HIDD and PE-HIDD (isolated from ABCR knockout mouse retinas), condensation products of all-trans-retinal and ethanolamine and phosphatidylethanolamine, respectively. These compounds are likely precursors for A2-E formation, as is A2-PE. The data for PE-HIDD are preliminary, as are data from a study of optimum synthetic conditions for A2-PE.; Time resolved and steady state techniques have been used to examine the photophysical properties of HIDD, protonated HIDD (HIDD-H+) and PE-HIDD and to determine the photoreactivities of these compounds and RAL towards several suitable substrates. The lifetime of the RAL triplet excited state is observed to decrease with increasing concentration of the well known electron and hydrogen atom donors, 2,3,5,6-tetramethyl-1,4-phenylenediamine (DAD), hydroquinone (HQ), methylhydroquinone (MHQ), 2,3-dimethylhydroquinone (DMHQ), and trimethylhydroquinone (TMHQ), although the bimolecular rate constants for reaction are much less than diffusion controlled (2.9 × 10 7 M−1s−1, 1.2 × 10 5 M−1s−1, 1.2 × 10 5 M−1s−1, 1.5 × 10 5 M−1s−1, and 1.6 × 106 M−1s−1, for DAD, HQ, MHQ, DMHQ, and TMHQ, respectively). Similar behavior is seen with HIDD and PE-HIDD in the presence of TMHQ and DAD. The bimolecular quenching rate constants (k_q) for HIDD are approximately 1.7 × 10 8 M−1s−1 and 5.4 × 106 M−1s−1 for TMHQ and DAD, respectively. Likewise, the k_qs for PE-HIDD are approximately 1.3 × 107 M−1s−1 and 2.0 × 107 M−1s−1 for TMHQ and DAD, respectively. HIDD and PE-HIDD produce singlet oxygen upon direct excitation. These types of reactions may model photooxidative mechanisms of damage in the retina.