Drusen are extra-cellular deposits that form between the retinal pigment epithelium (RPE) and Bruch's membrane (BM). Numerous and/or confluent drusen are a significant risk factor for age-related macular degeneration (AMD). Here, using whole mounted human RPE preparation we show that RPE cell morphology changes in association with drusen. These changes included an increase in cell size and distortion in the regularity of their distribution. Further, although binucleation is relatively rare in human RPE, there was a marked increase in the number of binucleated RPE cell associated with individual druse. Surprisingly many of these changes were found at distances up to 400 mu m from drusen. (C) 2008 Elsevier Ltd. All rights reserved.