Retina-specific expression of PDGF-B versus PDGF-A: vascular versus nonvascular proliferative retinopathy.
OBJECTIVE
Platelet-derived growth factor (PDGF) has been implicated in vascular proliferative retinopathies, such as diabetic retinopathy, and in nonvascular retinopathies, such as proliferative vitreoretinopathy. Traction retinal detachment is a central feature of both types of disease. Hemizygous rhodopsin promoter/PDGF-B (rho/PDGF-B) transgenic mice exhibit proliferation of vascular cells, glia, and retinal pigmented epithelial (RPE) cells, resulting in traction retinal detachment. Hemizygous rho/PDGF-A transgenic mice show mild proliferation of glial cells and no traction retinal detachments. This study was undertaken to determine whether higher levels of endogenously produced PDGF-A in the retinas of mice result in retinal detachment.


METHODS
To achieve high-level expression of PDGF-A in the retina, homozygous rho/PDGF-A (rho/PDGF-AA) mice were generated. The phenotype of these mice was compared with that of homozygous rho/PDGF-B (rho/PDGF-BB) mice and double hemizygous rho/PDGF-B-rho/PDGF-A (rho/PDGF-AB) mice.


RESULTS
Rho/PDGF-BB and rho/PDGF-AB mice showed a phenotype similar to that previously described in rho/PDGF-B mice. There was extensive proliferation of glial and vascular cells, resulting in fibrovascular membranes that detached the retina. PDGF-AA mice showed extensive proliferation of glial cells and traction retinal detachment.


CONCLUSIONS
High retinal expression of PDGF-A results in extensive proliferation of glial cells and traction retinal detachment without vascular cell involvement, similar to proliferative vitreoretinopathy in humans. High retinal expression of PDGF-B results in traction retinal detachment from proliferation of both vascular and nonvascular cells, similar to diabetic retinopathy in humans.
Mori
Keisuke
K
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA.
Gehlbach
Peter
P
Ando
Akira
A
Dyer
Gawain
G
Lipinsky
Evan
E
Chaudhry
Aneeka G
AG
Hackett
Sean F
SF
Campochiaro
Peter A
PA
D000818:Animals; D002455:Cell Division; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis / Q000502:physiology*; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012163:Retinal Detachment / Q000378:metabolism* / Q000473:pathology; D019076:Transgenes; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism* / Q000473:pathology
D005904:Glial Fibrillary Acidic Protein; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A