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Jeevan R. Mathura, Nadereh Jafari, Jinghua T. Chang, Sean F. Hackett, Karl J. Wahlin, Neil G. Della, Naoyuki Okamoto, Donald J. Zack, Peter A. Campochiaro; Bone Morphogenetic Proteins-2 and -4: Negative Growth Regulators in Adult Retinal Pigmented Epithelium. Invest. Ophthalmol. Vis. Sci. 2000;41(2):592-600.
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purpose. To determine the relative level and localization of bone morphogenetic
protein (BMP)-4 mRNA in the retina and retinal pigmented epithelium
(RPE) under normal and pathologic conditions, to seek clues regarding
methods. Clones isolated from an RPE cDNA library were sequenced and used as
probes for northern blot analysis. Expression in the retina and RPE was
investigated in mouse models using reverse transcription–polymerase
chain reaction (RT-PCR) and in situ hybridization. The effect of
recombinant proteins on RPE proliferation was investigated by thymidine
results. Bovine clones with high homology to BMP-2 and BMP-4 were isolated from
a subtracted RPE cDNA library. Northern blot analysis using the clones
as probes demonstrated abundant and differential expression in adult
bovine RPE, but with RT-PCR and in situ hybridization, expression was
also demonstrated in mouse retinal neurons. In mice with oxygen-induced
ischemic retinopathy there was a striking decrease in BMP-4 mRNA in the
retina within 6 hours of the onset of hypoxia that was maintained for
at least 5 days. In mice with inherited photoreceptor degeneration,
there was a dramatic decrease in BMP-4 mRNA in retina and RPE during
and after the degeneration. mRNA for the type II BMP receptor was
observed in freshly isolated and cultured RPE cells, isolated retina,
and freshly isolated bovine aortic endothelial cells. Thymidine
incorporation in early-passage RPE cells showed a 14-fold stimulation
above control with 5% serum that was decreased to 322%, 393%, and
313% in the presence of BMP-2 (10 ng/ml), BMP-4 (10 ng/ml), and
transforming growth factor (TGF)-β1 (2 ng/ml), respectively.
conclusions. BMP-2 and BMP-4 may serve as negative growth regulators in the retina
and RPE that are downregulated by injury, to allow tissue repair.
Modulation of expression of the BMPs may provide a means to control the
exaggerated wound repair that occurs in proliferative
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