TY - JOUR
T1 - Photoreceptor-specific overexpression of platelet-derived growth factor induces proliferation of endothelial cells, pericytes, and glial cells and aberrant vascular development
T2 - An ultrastructural and immunocytochemical study
AU - Vinores, Stanley A.
AU - Seo, Man Seong
AU - Derevjanik, Nancy L.
AU - Campochiaro, Peter A.
N1 - Funding Information:
This study was supported by grants EY05951 and EY10017 from the National Eye Institute, National Institutes of Health, by Lew R. Wasserman Merit Awards (SAV, PAC) presented by Research to Prevent Blindness, and by an unrestricted grant from Research to Prevent Blindness. We would like to thank Drs. P. Overbeek (Houston, TX) and J. Ash (Oklahoma City, OK) for useful discussions that contributed to the composition of this manuscript.
PY - 2003/2/16
Y1 - 2003/2/16
N2 - Platelet-derived growth factor (PDGF) is necessary for the normal development of the retinal vasculature and its overexpression is likely to contribute to proliferative retinal disorders, such as proliferative vitreoretinopathy. Transgenic mice that overexpress PDGF-B in the photoreceptors (rho/PDGF-B mice) develop traction retinal detachment. In the present study, a detailed histopathological analysis was performed in rho/PDGF-B mice. In these transgenic mice, endothelial cells, pericytes, and glial cells begin to proliferate at postnatal day 7 (P7). All three cell types increase in numbers, forming a highly vascularized cell mass, which reaches a maximum thickness at P14. Cords of endothelial cells and glia invade the retina and exert traction, generating retinal folds; however, the deep capillary bed never forms. Griffonia simplicifolia isolectin B4 (GSA)-positive endothelial cells form tubes and penetrate the retina to the level of the outer plexiform layer, but they never interconnect to form the deep capillary bed. The vessels within the cell mass are patent, but have a very immature morphology. They often are thin-walled with fenestrations. Pericytes and glial cells are usually found in clusters and are not associated with the abnormal vessels. The lack of this association may account for the failure to form a mature vasculature.
AB - Platelet-derived growth factor (PDGF) is necessary for the normal development of the retinal vasculature and its overexpression is likely to contribute to proliferative retinal disorders, such as proliferative vitreoretinopathy. Transgenic mice that overexpress PDGF-B in the photoreceptors (rho/PDGF-B mice) develop traction retinal detachment. In the present study, a detailed histopathological analysis was performed in rho/PDGF-B mice. In these transgenic mice, endothelial cells, pericytes, and glial cells begin to proliferate at postnatal day 7 (P7). All three cell types increase in numbers, forming a highly vascularized cell mass, which reaches a maximum thickness at P14. Cords of endothelial cells and glia invade the retina and exert traction, generating retinal folds; however, the deep capillary bed never forms. Griffonia simplicifolia isolectin B4 (GSA)-positive endothelial cells form tubes and penetrate the retina to the level of the outer plexiform layer, but they never interconnect to form the deep capillary bed. The vessels within the cell mass are patent, but have a very immature morphology. They often are thin-walled with fenestrations. Pericytes and glial cells are usually found in clusters and are not associated with the abnormal vessels. The lack of this association may account for the failure to form a mature vasculature.
KW - Blood-retinal barrier
KW - Endothelial cell
KW - Glia
KW - Pericytes
KW - Platelet-derived growth factor
KW - Retinal neovascularization
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U2 - 10.1016/S0165-3806(02)00581-3
DO - 10.1016/S0165-3806(02)00581-3
M3 - Article
C2 - 12586423
AN - SCOPUS:0037448755
SN - 0165-3806
VL - 140
SP - 169
EP - 183
JO - Developmental Brain Research
JF - Developmental Brain Research
IS - 2
ER -