Hematogenous photosensitization. A mechanism for the development of age-related macular degeneration.
Age-related macular degeneration (ARMD) is one of the leading causes of severe visual loss in the United States. Numerous risk factors have been investigated, but the pathogenesis of ARMD has remained elusive. The authors propose that ARMD develops as a direct result of photosensitization of the vascular endothelium of the choriocapillaris, Bruch's membrane, and the retinal pigment epithelium (RPE) by superoxide anion and singlet oxygen generated by photoactive compounds in blood. Using electron-spin resonance spectrometry, the free-radical trap, 5,5-dimethyl-1-pyrroline-N-oxide, and the singlet-oxygen trap, 2-(9,10-dimethoxyanthracentyl)-t-butylhydroxylamine, the authors demonstrate that the photoactive compound, protoporphyrin IX (PP IX), a naturally occurring precursor molecule of hemoglobin found in erythrocytes and plasma, generates superoxide anion and singlet oxygen. The amount of reactive-oxygen species produced by this system is dependent on the concentration of PP IX and the intensity and wavelength of the light delivered. Furthermore, the production of these photooxidants is significantly reduced by filtering the excitatory wavelengths of PP IX. These photogenerated oxidants could damage the vascular endothelium of the choriocapillaris, Bruch's membrane, and the RPE, necessitating a reparative process. This could result in features characteristically seen in ARMD such as a thickened Bruch's membrane, RPE atrophy, and hyperplasia. Prevention of phototoxic damage by this mechanism could involve enhancing protective enzymes, increasing scavenger substances, or supplying appropriate filters to eliminate the exciting wavelengths of light.
Gottsch
J D
JD
Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD 21205.
Pou
S
S
Bynoe
L A
LA
Rosen
G M
GM
D000375:Aging / Q000502:physiology; D000873:Anthracenes; D003497:Cyclic N-Oxides / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D008027:Light; D008268:Macular Degeneration / Q000209:etiology*; D011524:Protoporphyrins / Q000378:metabolism*; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism
D000873:Anthracenes; D003497:Cyclic N-Oxides; D011524:Protoporphyrins; D013113:Spin Labels; D013481:Superoxides; C017245:5,5-dimethyl-1-pyrroline-1-oxide; C052113:2-(9,10-dimethoxyanthracenyl)-tert-butylhydroxylamine; C028025:protoporphyrin IX