The human retina and retinal pigment epithelium are abundant sources of vitronectin mRNA

Vitronectin (Vn), a multifunctional plasma protein synthesized primarily in the liver, is often present as a component of the extracellular plaques an d deposits that accompany various age-related human diseases. Recently, we reported that Vn is also a prominent molecular constituent of drusen, the e xtracellular deposits associated with age-related macular degeneration (AMD ) (1), The cellular source(s) of the Vn in drusen, as well as in these othe r plaques and deposits, remains uncertain. In this study, we used real-time quantitative RT-PCR to measure the relative levels of Vn mRNA in the cells and tissues that lie in close proximity to drusen. The results confirm tha t the human liver is an abundant source of Vn mRNA. Levels of Vn mRNA in ki dney, lung, and fetal or adult brain are <3% of those in liver. Remarkably, mean Vn mRNA levels in the neural retina significantly exceed those in bra in and represent close to 40% of the Vn mRNA value measured in human liver. Substantial levels of Vn mRNA are also present in the adjacent retinal pig ment epithelium (RPE), These results identify the neural retina, for the fi rst time, as an abundant source of Vn mRNA, They also suggest that both the neural retina and RPE are potent biosynthetic sources of Vn in humans, and potentially significant local contributors to the Vn that accumulates in d rusen. (C) 1999 Academic Press.