New at Insight
NEW ARTICLESFor past Eyeware articles, visit our Eyecare News Archive |
Update on Macular Degeneration-Scientific articleCreated:01/06/2007Investigators in , Scotland and the United States have published new macular degeneration data.Study 1: Scientists discuss in "Iron induced oxidative damage as a potential factor in age-related macular degeneration: the Cogan Lecture" new findings in macular degeneration. According to recent research published in the journal Investigative Ophthalmology & Visual Science, "Iron is a potent generator of oxidative damage whose levels increase with age, potentially exacerbating age-related diseases. Several lines of evidence suggest that iron accumulation may be a factor in age-related macular degeneration (AMD)." "AMD retinas have more iron within the photoreceptors, RPE, and drusen than do age-matched control retinas. Accelerated AMD-like maculopathy develops in patients with retinal iron overload from the hereditary disease aceruloplasminemia. Mice with retinal iron overload resulting from knockout of ceruloplasmin and its homologue hephaestin exhibit retinal degeneration with some features of AMD, including subretinal neovascularization, accumulation of RPE lipofuscin and sub-RPE deposits, and RPE/photoreceptor death. Increased understanding of the mechanisms of retinal iron homeostasis may help in the development of therapies to prevent iron overload. For example, herein it is shown that one regulator of systemic iron homeostasis, HFE, is expressed in the RPE. Thus, patients with the common disease hereditary hemochromatosis, which is often caused by an HFE mutation, may have retinal iron overload predisposing to AMD," wrote J.L Dunaief and colleagues, Scheie Eye Institute. The researchers concluded: "Preliminary data suggest that iron chelation can reduce RPE iron overload in mice and protect them from degeneration, suggesting that iron-binding drugs may one day prove useful in reducing RPE oxidative stress and decreasing the risk of AMD progression." Dunaief and colleagues published their study in Investigative Ophthalmology & Visual Science (Iron induced oxidative damage as a potential factor in age-related macular degeneration: the Cogan Lecture. Investigative Ophthalmology & Visual Science, 2006;47(11):4660-4). For additional information, contact J.L. Dunaief, University of Pennsylvania, F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, 305 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104 U.S. Study 2: Late-onset retinal macular degeneration (L-ORMD) is linked to C1QTNF5 mutation. According to recent research from Scotland, "L-ORMD is an autosomal dominant condition resembling age-related macular degeneration (AMD) in which a key pathological feature is a thick extracellular sub-retinal pigment epithelial (RPE) deposit. L-ORMD is caused by mutation in the C1QTNF5 (CTRP5) short-chain collagen gene, but the disease mechanism is unknown." "Here, we first show that wild-type C1QTNF5 is secreted, whereas mutant C1QTNF5 is misfolded and retained within the endoplasmic reticulum (ER). Secondly, the ER retained mutant protein has a shorter half-life than wild-type C1QTNF5 and is preferentially degraded by proteasomes," said X.H. Shu and colleagues, Western General Hospital. "Thirdly," they noted, "C1QTNF5 is shown to interact with the membrane-type frizzled related protein (MFRP), on the basis of yeast two-hybrid, protein pull-down and co-immunoprecipitation assays and RPE co-localization. These data suggest that L-ORMD is due to insufficient levels of secreted C1QTNF5, compromised RPE cell function resulting from ER retention of the mutant protein, or both mechanisms." Shu and colleagues published their study in Human Molecular Genetics (Disease mechanisms in late-onset retinal macular degeneration associated with mutation in C1QTNF5. Hum Mol Genet, 2006;15(10):1680-1689). For additional information, contact X.H. Shu, Western General Hospital, Medical Research Council, Human Genetics Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Study 3: Lipid efflux from retinal pigment epithelial cells (RPE) is influenced by high density lipoprotein (HDL). "The transport of radiolabelled photoreceptor outer segments (POS) lipids was investigated by cultured RPE. Phagocytosis of POS by the RPE is essential to maintain the health and function of the photoreceptors in vivo," investigators in the United States report. B.Y. Ishida and colleagues, University of California, San Francisco, explained, "POS are phagocytised at the apical cell surface of RPE cells. Phagocytised POS lipids may be either recycled to the photoreceptors for reincorporation into new POS or they may be transported to the basolateral surface for efflux into the circulation. "The authors have demonstrated that HDL stimulates efflux of radiolabeled lipids, of POS origin, from the basal surface of RPE cells in culture. Effluxed lipids bind preferentially to HDL species of low and high molecular weight. Effluxed radiolabeled phosphotidyl choline was the major phospholipid bound to HDL, with lesser amounts of phosphatidyl ethanolamine, phosphatidyl inosotol. Effluxed radiolabelled triglycerides, cholesterol, and cholesterol esters also bound to HDL." "Lipid free apolipoprotein A-I (apoA-I) and apoA-I containing vesicles also stimulate lipid efflux. The findings suggest a role for HDL and apoA-I in regulating lipid and cholesterol transport from RPE cells that may influence the pathological lipid accumulation associated with age related macular degeneration," scientists suggested. Ishida and colleagues published their study in British Journal of Ophthalmology (High density lipoprotein mediated lipid efflux from retinal pigment epithelial cells in culture. Br J Ophthalmol, 2006;90(5):616-620). For additional information, contact D.M. Schwartz, University of California San Francisco, Dept. Ophthalmology, Box 0730, San Francisco, CA 94143, USA. |