Open AccessIn vitro drusen model: three-dimensional spheroid culture of retinal pigment epithelial cells
Author(s) -
Hideaki Usui,
Akiko Nishiwaki,
Lanors Landiev,
Johannes Kacza,
Wolfdietrich Eichler,
Rina Wako,
Aki Kato,
Noriaki Takase,
Soichiro Kuwayama,
Katsuhisa Ohashi,
Yousef Yafai,
Andreas Bringmann,
Ayae Kubota,
Yuichiro Ogura,
Johannes Seeger,
Peter Wiedemann,
Tsutomu Yasukawa
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.215798
Subject(s) - biology , drusen , spheroid , in vitro , retinal , microbiology and biotechnology , retinal pigment epithelium , botany , biochemistry
Age-related macular degeneration (AMD) is a leading cause of legal blindness in people over 50 years of age in many developed countries. Drusen are yellowish extracellular deposits beneath retinal pigment epithelium (RPE) found in aging eyes and considered as a biomarker of AMD. However, the biogenesis of drusen has not been elucidated. We reported previously that multicellular spheroids comprised of human RPE cells constructed a well-differentiated monolayer of RPE with Bruch's membrane. We determined that RPE spheroids exhibited drusen formation between RPE and Bruch's membrane with expression of many drusen-associated proteins such as amyloid ß and complement components, the expression of which was altered by a challenge with oxidative stress. Artificial lipofuscin-loaded RPE spheroids yielded drusen more frequently. In the current study, we showed that drusen originates from the RPE. This culture system is an attractive tool for use as an in vitro drusen model, which might help elucidate the biogenesis of drusen and the pathogenesis of related diseases such as AMD.