Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes.
OBJECTIVE
To determine the cellular origin and the vascular endothelial growth factor (VEGF) immunoreactivity of the nonvascular stromal cells in surgically excised age-related macular degeneration (ARMD)-associated choroidal neovascular membranes (CNVMs).


METHODS
Immunohistochemical analysis was performed on frozen sections of eight surgically excised ARMD-related CNVMs.


RESULTS
Cytokeratin-positive, smooth muscle actin-positive polygonal or fibroblastic (transdifferentiated RPE) cells were the principal nonvascular stromal cells detected. The polygonal cells were more commonly found in active (highly vascularized) regions and were strongly immunoreactive for VEGF. The fibroblastic cells were predominantly found in fibrotic (hypovascular) regions and were minimally immunoreactive for VEGF.


CONCLUSIONS
Transdifferentiated RPE cells are the principal nonvascular stromal cells of both vascular and fibrotic ARMD-related CNVMs. Preferential localization of VEGF immunoreactivity with the cytoplasm of the polygonal transdifferentiated RPE cells in the highly vascularized regions of the surgically excised CNVMs suggests an important angiogenic role of these cells and this growth factor in the progression of ARMD-related choroidal neovascularization.
Lopez
P F
PF
Department of Ophthalmology, University of Southern California, Los Angeles, CA 90033, USA.
Sippy
B D
BD
Lambert
H M
HM
Thach
A B
AB
Hinton
D R
DR
D000199:Actins / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D002454:Cell Differentiation; D002829:Choroid / Q000098:blood supply* / Q000601:surgery; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000378:metabolism; D008222:Lymphokines / Q000032:analysis* / Q000276:immunology; D008268:Macular Degeneration / Q000150:complications*; D008297:Male; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D010857:Pigment Epithelium of Eye / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000199:Actins; D000911:Antibodies, Monoclonal; D016228:Endothelial Growth Factors; D005904:Glial Fibrillary Acidic Protein; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D007633:Keratins