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N. Tanaka, M. Ikawa, K. Bessho, W.R. Freeman, I.M. Verma; Prokineticin 1 induces choroidal angiogenesis but not retinal angiogenesis; a possible model for the pathogenesis of age–related macular degeneration . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1820.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The pathogenesis of age–related macular degeneration (AMD) is not fully understood. Recently prokineticin 1 (hPK1) was identified as a mitogen specific for the fenestrated endothelium. We hypothesized that hPK1 could induce choroidal neovascularization (CNV) without retinal angiogenesis, because the endothelium of choriocapillaris, but not retinal endothelium, has fenestrated phenotype. To verify the hypothesis we performed both in vitro and in vivo experiment. Methods: We performed RT–PCR to detect mRNA of hPKs and their receptors, hPKRs in both retinal pigment epithelial cell line (RPE) and retinochoroidal endothelial cell line (RCEC). Cell viability and signal transduction induced by hPKs was examined by MTT assay and Western blot analysis respectively. To see the effect of hPK1 in the eye, transgenic mouse was generated and their phenotype was evaluated by fluorescein angiography and histology. The level of hPK1 in vitreous samples from AMD patients was assessed by Western blot analysis. Results: First, we detected transcripts of hPK1 and its homologue hPK2, and their receptors, hPKR1 and hPKR2, in both RPE and RCEC. Second, we found that the viability of RCEC expressing hPK1 and hPK2 transduced by lentiviral vectors was increased possibly through the activation of Akt and/or ERK kinases. Surprisingly we also found that the viability of RPE cells expressing hPK1 was decreased via inhibition of ERK activation. Third, we could observe choroidal angiogenesis, but not retinal angiogenesis, in the transgenic mice that overexpressed hPK1 in retina. Finally, hPK1 levels in vitreous samples from AMD patients and proliferative diabetic retinopathy patients were elevated compared to those from control patients. Conclusions: According to these results, we offer a novel concept for the pathogenesis of AMD that increased hPK1 might damage RPE cells and induce CNV in the diseased eyes.
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