Retinal degeneration triggered by inactivation of PTEN in the retinal pigment epithelium.
Adhesion between epithelial cells mediates apical-basal polarization, cell proliferation, and survival, and defects in adhesion junctions are associated with abnormalities from degeneration to cancer. We found that the maintenance of specialized adhesions between cells of the retinal pigment epithelium (RPE) requires the phosphatase PTEN. RPE-specific deletion of the mouse pten gene results in RPE cells that fail to maintain basolateral adhesions, undergo an epithelial-to-mesenchymal transition (EMT), and subsequently migrate out of the retina entirely. These events in turn lead to the progressive death of photoreceptors. The C-terminal PSD-95/Dlg/ZO-1 (PDZ)-binding domain of PTEN is essential for the maintenance of RPE cell junctional integrity. Inactivation of PTEN, and loss of its interaction with junctional proteins, are also evident in RPE cells isolated from ccr2(-/-) mice and from mice subjected to oxidative damage, both of which display age-related macular degeneration (AMD). Together, these results highlight an essential role for PTEN in normal RPE cell function and in the response of these cells to oxidative stress.
Kim
Jin Woo
JW
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea. jinwookim@kaist.ac.kr
Kang
Kyung Hwa
KH
Burrola
Patrick
P
Mak
Tak W
TW
Lemke
Greg
G
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002478:Cells, Cultured; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008954:Models, Biological; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse