Platelet-derived growth factor D, tissue-specific expression in the eye, and a key role in control of lens epithelial cell proliferation.
Platelet-derived growth factor D (PDGF-D), also known as Iris-expressed growth factor, is a member of the PDGF/vascular endothelial growth factor family. The expression of PDGF-D in the eye is tissue-specific. In the anterior segment, it is localized to iris and ciliary body, whereas in the retina, PDGF-D is restricted to the outer plexiform layer. PDGF-D is present in aqueous humor but is not detectable in mature lens or in mouse lens-derived alphaTN4-1 cells. However, it is expressed in rabbit lens-derived N/N1003A cells. N/N1003A cell-conditioned medium stimulates proliferation in rat lens explants, and this is blocked by immunodepletion of PDGF-D. Immunopurified PDGF-D also stimulates cell proliferation in rat lens explants and in NIH 3T3 cells. In organ culture of rat eye anterior segments, anti-PDGF-D strongly inhibits lens epithelial cell proliferation. This finding suggests a major in vivo role for PDGF-D in the mechanisms of coordinated growth of eye tissues. Intervention in the PDGF-D pathway in the eye, perhaps by antibody or blocking peptide, could be useful in the treatment of certain cataracts, including post-operative secondary cataract.
Ray
Sugata
S
NEI, National Institutes of Health, Bethesda, Maryland 20892-0703, USA.
Gao
Chun
C
Wyatt
Keith
K
Fariss
Robert N
RN
Bundek
Amanda
A
Zelenka
Peggy
P
Wistow
Graeme
G
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology*; D005123:Eye / Q000378:metabolism*; D000882:Haplorhini; D007498:Iris / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology* / Q000378:metabolism*; D008222:Lymphokines / Q000096:biosynthesis*; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D010455:Peptides / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis*; D011817:Rabbits; D051381:Rats; D012160:Retina / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D017077:Culture Media, Conditioned; D008222:Lymphokines; C498951:Pdgfd protein, mouse; C498952:Pdgfd protein, rat; D010455:Peptides; D010982:Platelet-Derived Growth Factor; C411423:platelet-derived growth factor C