Impaired intracellular signaling may allow up-regulation of CTGF-synthesis and secondary peri-retinal fibrosis in human retinal pigment epithelial cells from patients with age-related macular degeneration.
Age-related macular degeneration (AMD) is a major sight-threatening ocular disorder in the United States of America and the world, yet its etiology is not clearly understood, preventing the development of effective prevention or therapy. Connective tissue growth factor (CTGF) has been implicated in the pathological synthesis of peri-retinal fibrous tissue in patients with AMD. Very little is known about the mechanism of this interaction. In this study, the authors demonstrate that insulin like growth factor-1 (IGF-1) and glucose-stimulated CTGF production are not blocked by the MAP kinase pathway inhibitor, PD98059 in hRPE cells obtained from eyes of a patient with AMD in contrast to hRPE cells obtained from normal human eyes. This suggests that there may be abnormal CTGF synthesis regulation in AMD, which may play a role in fibrous peri-retinal membrane formation in patients with AMD-related proliferative vitreoretinopathy.
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA.
Piyush C
PC
Kothary
Jaya
J
Badhwar
Christina
C
Weng
Monte A
MA
Del Monte
D002250:Carbon Radioisotopes; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D005419:Flavonoids / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D008268:Macular Degeneration / Q000378:metabolism* / Q000473:pathology; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D002250:Carbon Radioisotopes; D005419:Flavonoids; D055513:Connective Tissue Growth Factor; D007334:Insulin-Like Growth Factor I; D005947:Glucose; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one