Research Perspective|Volume 1, Issue 8|pp 740—745

What determines the switch between atrophic and neovascular forms ofage related macular degeneration? - the role of BMP4 induced senescence

DanHong Zhu^1,², Xuemei Deng^1,², Jing Xu², David R Hinton^1,^2,³

¹Arnold and Mabel Beckman MacularResearch Center, Doheny Eye Institute, Los Angeles, CA 90033, USA
²Departments of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles CA 90089, USA
³Departmentsof Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles CA 90089, USA

Received: July 3, 2009Accepted: August 10, 2009Published: August 12, 2009

Copyright: © 2009 Zhu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Age-related macular degeneration (AMD), the leadingcause of blindness in the elderly, targets the retinal pigment epithelium(RPE), a monolayer of cells at the back of the eye. As AMD progresses, itcan 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 ofchoroidal vessels. The genetic and molecular pathways that lead to thesediverse phenotypes are currently under investigation. We have found thatbone morphogenetic protein-4 (BMP4) is differentially expressed in atrophicand neovascular AMD. In atrophic AMD, BMP4 is highly expressed in RPE, andmediates oxidative stress induced RPE senescencein vitro via Smadand p38 pathways. In contrast, in neovascular AMD lesions, BMP4 expressionin RPE is low, possibly a result of local expression of pro-inflammatorymediators. Thus, BMP4 may be involved in the molecular switch determiningwhich phenotypic pathway is taken in the progression of AMD.