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.