Oxidized phospholipids in the macula increase with age and in eyes with age-related macular degeneration.
OBJECTIVE
There is good evidence that oxidative stress is involved in the pathogenesis of age-related macular degeneration (AMD). Because AMD has risk factors and histopathology similar to with atherosclerosis, we hypothesized that oxidized phospholipids, which contribute to the pathogenesis of atherosclerosis, would accumulate in the eyes of AMD patients. To test this hypothesis, we investigated whether oxidized phospholipids were present in normal eyes and whether the level changed with increasing age. We then, we determined whether the levels of oxidized phospholipids were higher in eyes with AMD.


METHODS
Twenty normal human donor eyes and six eyes with AMD were studied. Immunohistochemistry was performed on a tissue strip from the macular region using an antibody against oxidized phosphatidylcholine. Western blot analysis was also performed on proteins extracted from the posterior retina of donor eyes. The immunoreactivity of the specimens and the bands were quantified with NIH image software.


RESULTS
Immunohistochemistry showed oxidized phosphatidylcholine was present in the photoreceptors and retinal pigment epithelium of the normal human macular area, and their levels increased with age. Eyes with AMD showed more intense immunoreactivity for oxidized phospholipids than age-matched normal eyes.


CONCLUSIONS
These findings suggest that oxidative stress is involved in the pathogenesis of AMD possibly by oxidizing phospholipids in the photoreceptors as demonstrated in the arterial intima of patients with atherosclerosis. It is likely that controlling oxidation of phospholipids may be a potential treatment for AMD.
Suzuki
Mihoko
M
Department of Ophthalmology, Osaka University Medical School, Suita, Japan. msuzuki@ophthal.med.osaka-u.ac.jp
Kamei
Motohiro
M
Itabe
Hiroyuki
H
Yoneda
Kazuhito
K
Bando
Hajime
H
Kume
Noriaki
N
Tano
Yasuo
Y
D000375:Aging / Q000378:metabolism*; D015153:Blotting, Western; D006801:Humans; D007150:Immunohistochemistry; D008268:Macular Degeneration / Q000378:metabolism*; D008875:Middle Aged; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D014018:Tissue Distribution
D010713:Phosphatidylcholines; D010743:Phospholipids