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J. A. Mocko, J. D. Akula, I. Y. Benador, A. Di Nardo, R. M. Hansen, A. B. Fulton; Expression of ‘Neural’ Growth Factors Directs Angiogenesis Early in the Course of ROP. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2633.
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To determine if retinal neurons, rendered dysfunctional by exposure to abnormal oxygen levels during their differentiation and development, promote growth factors that produce the tortuous arterioles that are the ‘clinical hallmark’ of ROP.
Retinopathy was induced in Sprague-Dawley rats (n=12) by exposure of pups to alternating 50%-10% oxygen from the day of birth (P0) to P14. Following a cross-sectional design, with tests at P15-16, P18-19, and P25-26, electroretinograms (ERGs) and digital fundus photographs were obtained. The retinae were then excised. Sensitivity of the rod photoreceptors (Sa) and the post-receptor neural retina (Sb) was assessed by respective evaluation of the ERG a- and b-waves. Arteriolar tortuosity (AT), defined as the integrated curvature of the arterioles, was determined by image analysis of the fundus photographs. mRNA of VEGF and semaphorin 3A (Sema3A), and their neuropilin receptors (NRP-1, -2), was amplified by RT-PCR and expressed as a proportion of GAPDH; fold-normal for age mRNA expression was calculated. Pearson correlation (R) was used to detect interrelations between neural function (Sa, Sb), growth factor mRNA expression, and AT.
At the youngest tested age (P15-16), expression of ‘neural’ growth factors (NRP-1, NRP-2, and Sema3A) was significantly correlated with AT (all P<0.05). Only Sema3A and NRP-2 expression were correlated with neural sensitivity parameters (Sa, Sb). At this youngest age, VEGF was not correlated with AT or neural sensitivity. Over the whole range of tested ages, both AT and VEGF declined, while sensitivity parameters, both receptor and post-receptor, increased.
In the early stages of ROP, the vascular abnormality that is the clinical hallmark of the disease appears to be under the control of ‘neural’ growth factors. Thus, neuroprotection of the immature retina is a promising therapeutic approach.
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