Age-related macular degeneration (AMD) represents the most common cause of blindness in patients over the age of 60. While both hereditary and environmental factors appear to play a role in the pathogenesis of the disease, no common genetic mutations have been identified. Based on laboratory evidence, one proposed hypothesis for this disease focuses on an altered injury response program of the retinal pigment epithelium. A clinical trial has now been completed which is testing this hypothesis that patterns of gene expression involved in wound repair, cell injury and death are altered in the eyes of patients with AMD and these genetic alterations can be detected in peripheral sites other than the eye. Biopsied skin fibroblasts from 7 patients with various forms of age-related macular degeneration and 3 age-matched control patients were obtained, grown in culture and exposed to a sublethal oxidative stress. RNA from these cells were examined and differential expression of a 15,000 genes was analyzed using a gene chip. Results were confirmed by quantitative RT-PCR. The results indicate a marked difference in gene expression profile between these groups of patients. Specifically, patients with more severe forms of AMD had a greater disregulation of affected compared with minimally affected and age-matched control patients. These results indicate that an abnormal response to injury may play a role in the pathogenesis of AMD.
| Hathout, Yetrib; Flippin, Jessica; Fan, Chenguang et al. (2005) Metabolic labeling of human primary retinal pigment epithelial cells for accurate comparative proteomics. J Proteome Res 4:620-7 |
| Strunnikova, Nataly; Hilmer, Sara; Flippin, Jessica et al. (2005) Differences in gene expression profiles in dermal fibroblasts from control and patients with age-related macular degeneration elicited by oxidative injury. Free Radic Biol Med 39:781-96 |
| Cousins, Scott W; Espinosa-Heidmann, Diego G; Csaky, Karl G (2004) Monocyte activation in patients with age-related macular degeneration: a biomarker of risk for choroidal neovascularization? Arch Ophthalmol 122:1013-8 |
| Strunnikova, Nataly; Zhang, Connie; Teichberg, Diane et al. (2004) Survival of retinal pigment epithelium after exposure to prolonged oxidative injury: a detailed gene expression and cellular analysis. Invest Ophthalmol Vis Sci 45:3767-77 |
