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J. A. Mocko, T. L. Favazza, I. Y. Benador, R. M. Hansen, A. B. Fulton, J. D. Akula; Temporal Course of VEGF mRNA and Protein Expression in a Rat Model of Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3120.
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To characterize the temporal course of VEGF mRNA and protein expression in a system in which the retinal vasculature and receptor and post-receptor function can be manipulated. The goal is to determine the optimal timing of pharmaceutical interventions in ROP.
We induced retinopathy in Sprague-Dawley rats (n=12) by exposing newborn pups to alternating 50% and 10% oxygen for two weeks from the day of birth (‘ROP rats’). We also studied room-air-reared control rats (n=12). Following a cross-sectional design, with tests at postnatal day (P) 15 and P19, we obtained digital fundus photographs from both eyes before excising the retinae for analysis of VEGF. VEGF mRNA was quantified by reverse-transcriptase polymerase chain reaction (RT-PCR) and VEGF protein content was assessed by enzyme-linked immunosorbent assay (ELISA). All data were expressed as delta-log-normal for age. Students t-tests, corrected for the Bonferonni inequality (/2), were used to detect differences between groups at each age. Pearson correlation (R) was used to detect interrelations between VEGF mRNA and protein levels.
At P15, Δlog-normal VEGF mRNA was significantly elevated in ROP rats (P=0.007), as was VEGF protein (P=0.01). ΔLog-normal VEGF mRNA was linearly associated (R=0.80, P=0.001) with Δlog-normal VEGF protein with slope ~1.2. By P19, both VEGF mRNA and protein in ROP rats had fallen together and no longer differed significantly from controls. However, they were no longer linearly related.
VEGF levels change rapidly during the evolution and resolution of ROP. Changes to mRNA expression must precede changes in protein levels. Optimal timing of anti-VEGF pharmaceuticals will likely depend on description of the course of VEGF protein levels (not just mRNA), as well as the changing status of the neurovascular retina.
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