Abstract
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.
Highlights
AGING, August 2009, Vol.1 No.8 a genetic variant been identified that predisposes to the atrophic form [8]
We reported that bone morphogenetic protein (BMP)4 is prominently expressed in the retinal pigment epithelium (RPE) and adjacent extracellular matrix of patients with the dry or atrophic form of Age‐related macular degeneration (AMD) when compared to controls (Figure 2A, B)
We reported that bone morphogenetic protein‐4 (BMP4) can induce RPE senescence in vitro [11], and that RPE chronically exposed to sublethal doses of oxidative stress can increase their BMP4 expression and exhibit a senescent phenotype, supporting the contention that BMP4 mediates oxidative stress-induced RPE senescence
Summary
AGING, August 2009, Vol.1 No.8 a genetic variant been identified that predisposes to the atrophic form [8]. Pathogenic mechanisms for AMD include both genetic and environmental factors related to primary RPE senescence, alterations in the complement pathway, increased inflammation, changes in the balance of growth factors, excessive lipofuscin accumulation, and oxidative stress [5].
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