Premium
Gene transfer of E2F2 induces in situ regeneration of retinal pigment epithelium
Author(s) -
Luhmann U.,
Kampik D.,
Nishiguchi K.,
Basche M.,
Smith A.J.,
Ali R.R.
Publication year - 2016
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2016.0159
Subject(s) - retinal pigment epithelium , regeneration (biology) , microbiology and biotechnology , biology , retinal regeneration , retina , retinal , cell , in vivo , neuroscience , genetics , biochemistry
Summary The retinal pigment epithelium (RPE) interacts closely with photoreceptors and is important for maintaining visual function. In degenerative diseases such as age‐related macular degeneration (AMD), the leading cause of blindness in the developed world, RPE cell loss is followed by photoreceptor cell death. RPE cells can proliferate under certain conditions, suggesting an intrinsic regenerative potential, but so far this has not been utilised therapeutically. Here we use E2F2 , a potent transcriptional regulator of cell proliferation, to induce RPE regeneration in vitro and in vivo . Gene transfer of E2F2 induced upregulation of Ki67 and uptake of BrdU in growth arrested ARP19 cells in vitro . In both, young and old C57Bl/6 mice, subretinal lentiviral delivery of E2F2 to the RPE caused a 40‐fold ±27.2 increase in E2F2 positive RPE cells that correlated with a 10‐fold ±4.7 increase in BrdU positive cells and a mean increase of RPE cell density. E2F2 also induced BrdU uptake and increased cell density in the central RPE of RPE CreER /DTA mice, where pathology, induced by the activation of diphtheria toxin‐A, was strongest. These results provide proof of concept for a strategy to treat progressive RPE cell loss by in situ regeneration.