What determines the switch between atrophic and neovascular forms of age related macular degeneration? - the role of BMP4 induced senescence.
Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, targets the retinal pigment epithelium (RPE), a monolayer of cells at the back of the eye. As AMD progresses, it can develop into two distinct forms of late AMD: "dry," atrophic AMD, characterized by RPE senescence and geographic RPE loss, and "wet," neovascular AMD, characterized by RPE activation with abnormal growth of choroidal vessels. The genetic and molecular pathways that lead to these diverse phenotypes are currently under investigation. We have found that bone morphogenetic protein-4 (BMP4) is differentially expressed in atrophic and neovascular AMD. In atrophic AMD, BMP4 is highly expressed in RPE, and mediates oxidative stress induced RPE senescencein vitro via Smad and p38 pathways. In contrast, in neovascular AMD lesions, BMP4 expression in RPE is low, possibly a result of local expression of pro-inflammatory mediators. Thus, BMP4 may be involved in the molecular switch determining which phenotypic pathway is taken in the progression of AMD.
Zhu
Danhong
D
Arnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA 90033, USA.
Deng
Xuemei
X
Xu
Jing
J
Hinton
David R
DR
D000375:Aging / Q000378:metabolism / Q000473:pathology*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D016209:Interleukin-8 / Q000032:analysis; D008268:Macular Degeneration / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D015861:Retinal Neovascularization / Q000378:metabolism / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000473:pathology; D051785:Smad Proteins / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016209:Interleukin-8; D051785:Smad Proteins; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases