Prompted by an interest in identifying mechanisms linking factors implicated in AMD pathogenesis, including inflammation, oxidative damage, drusen, and retinal pigment epithelial (RPE) lipofuscin, we previously explored the possibility that products of the photooxidation of RPE lipofuscin pigments activate the complement system.
20 The lipofuscin of RPE cells accumulates with age, is generated primarily as a byproduct of retinoid cycling, and includes the bisretinoid compounds A2E, isoA2E, all-
trans-retinal dimer, all-
trans-retinal dimer-ethanolamine (all-
trans-retinal dimer-E), and all-
trans-retinal dimer-phosphatidylethanolamine (all-
trans-retinal dimer-PE).
21 22 23 24 These lipofuscin constituents are photoreactive molecules that absorb light in the visible range of the spectrum, generate reactive forms of oxygen, become oxidized, and undergo photo-induced fragmentation.
21 22 23 24 All these lipofuscin pigments have been detected and measured in human retinal pigment epithelium and in eyecups of mice with null mutations in
Abca4/Abcr,
25 26 27 28 the gene responsible for recessive Stargardt disease.
29 Mono- and bis-oxygenated photoproducts of A2E and all-
trans-retinal dimer (furano-A2E, peroxy-A2E, furano-all-
trans-retinal dimer, peroxy-all-
trans-retinal dimer) have also been identified.
27 28