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Susumu Ishida, Kei Shinoda, Shinichi Kawashima, Yoshihisa Oguchi, Yasunori Okada, Eiji Ikeda; Coexpression of VEGF Receptors VEGF-R2 and Neuropilin-1 in Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2000;41(7):1649-1656.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. To elucidate vascular endothelial growth factor (VEGF)-mediated
pathogenesis of fibrovascular proliferation in diabetic retinopathy.
methods. Fibrovascular tissues were obtained at vitrectomy from 22 cases with
proliferative diabetic retinopathy. The half-divided tissues were
processed for reverse transcription–polymerase chain reaction
(RT–PCR) analysis to examine the expression of VEGF isoforms and their
receptors. Paraffin sections of the other half were used for
immunohistochemistry for CD34, glial fibrillary acidic protein and
VEGF, and in situ hybridization for VEGF.
results. RT–PCR analysis demonstrated the expression of VEGF receptors VEGF-R1,
VEGF-R2, and neuropilin-1 in 12, 14, and 14 of 22 cases, respectively.
Notably, VEGF-R2 and neuropilin-1 were simultaneously expressed in the
identical 14 tissues. The isoform VEGF121 was
constitutively expressed in all the tissues examined, whereas the
expression of VEGF165 was confined to the 7 tissues that
also expressed VEGF-R2 and neuropilin-1. The vascular density of
fibrovascular tissues evaluated by immunohistochemistry for CD34 was
significantly higher in the cases with the expression of VEGF-R2 and
neuropilin-1 than in those without their expression
(P < 0.01), whereas VEGF-R1 expression had no such
relationship with the vascular density. The fibrovascular tissues that
expressed VEGF165 together with VEGF-R2 and neuropilin-1
were found in significantly younger patients (P <
0.01). In situ hybridization and immunohistochemical studies
demonstrated that glial cells in the fibrovascular tissues express and
conclusions. Coexpression of VEGF-R2 and neuropilin-1 is suggested to facilitate
fibrovascular proliferation in diabetic
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