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S. Ray, R. Fariss, K. Wyatt, P. Zelenka, G. Wistow; A Central Role for Iris-Expressed Growth Factor/PDGFD in Proliferation of Lens Epithelial Cells and Control of Lens Growth . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4501.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To examine the role of Iris-Expressed Growth Factor/PDGFD (IEGF) in the eye. Methods: Clones were obtained from EST analysis and by PCR methods. Rabbit antiserum IEGFp1 was raised against a specific IEGF peptide. IEGF expression was examined by western and northern blots and immunofluorescence (IF). IEGF protein was purified by immunoprecipitation (IP) from N/N1003A cell conditioned medium. IEGF activity was tested on rat lens explants and anterior segments and blocked with IEGFp1 serum. Results: IEGF (or PDGFD) is a novel member of the PDGF/VEGF family of growth factors. It was discovered in the eye through expressed sequence tag (EST) analysis of human iris in the NEIBank project. By IF, the IEGFp1 antiserum localizes IEGF to the posterior regions of iris and ciliary body opposite the proliferative zone of the lens in rodents and monkey, with low or absent expression in lens. The N/N1003A lens-cell derived line expresses high levels of IEGF, while the transformed αTN4-1 lens line has no expression. N/N1003A conditioned medium or IEGF purified by IP induces proliferation in newborn rat lens explants, while immuno-depleted medium or αTN4-1 conditioned medium has no significant effect. IEGFp1 antiserum also blocks lens cell proliferation in cultured rat anterior segments. Several receptors for PDGF/VEGF superfamily members are expressed in lens epithelium. Receptor binding studies are in progress. In addition to its specific localization in the anterior segment, IEGF shows localization to the OPL/ONL boundary in the retina. Conclusions: IEGF is expressed in a pattern consistent with a role in controlling lens growth. It is expressed at high levels in a lens-derived cell line, although not in native lens or in transformed lens-derived cells. Native IEGF produced from N/N1003A cells induces lens cell proliferation and antibody to IEGF can block proliferation in lens explants and in dissected anterior segments. This suggests that IEGF has a key role in lens cell proliferation and lens growth. Antibody or peptide intervention targeted at IEGF could be useful in suppressing secondary cataract. The expression of IEGF in retina suggests a possible role in the normal function of photoreceptors.
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