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(Investigative Ophthalmology and Visual Science. 2006;47:738-744.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-1046
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Ontogeny of VEGF, IGF-I, and GH in Neonatal Rat Serum, Vitreous Fluid, and Retina from Birth to Weaning

Houchang D. Modanlou,1 Zahra Gharraee,1,2 Jamal Hasan,1,2 Joshua Waltzman,3 Stephen Nageotte,3 and Kay D. A. Beharry1,2

1From the Division of Neonatal-Perinatal Medicine, University of California Irvine Medical Center, Orange, California; the 2Division of Neonatal-Perinatal Medicine, Miller Children’s Hospital, Long Beach, California; and the 3Memorial Health Services Research Center, Long Beach, California.

PURPOSE. Vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, and growth hormone (GH) are major regulators of physical growth, as well as normal and pathologic retinal development. Ocular tissues are protected by the blood–ocular barrier. This study was conducted to test the hypothesis that the ontogenic profiles of VEGF, IGF-I, and GH in the rat serum, vitreous fluid, and retina are compartment specific, and that the vitreous is a reservoir for retinal growth factors.

METHODS. Sprague-Dawley rat pups were killed at birth (postnatal day [P]0) and at P7, P14, and P21. At death, serum, vitreous fluid, and retinal homogenates were analyzed for ontogeny of VEGF, IGF-I, and GH.

RESULTS. VEGF levels were 10 times higher in the vitreous than in serum at all stages of development. Vitreous and serum VEGF levels progressively declined, with lowest concentrations at P21. Retinal VEGF levels increased with the highest concentration at P21. IGF-I levels in the vitreous decreased from P7 through P21. IGF-I levels in serum and retinal homogenates increased with advancing postnatal age. Although IGF-I levels were four times higher in the vitreous than in the retina at P0, equilibration was achieved at P21. GH levels in the vitreous were 10 times lower than serum levels, were decreased at P14 and P21, and remained unchanged from P0 through P21 in the retina.

CONCLUSIONS. VEGF and IGF-I act in concert to promote retinal development with the vitreous fluid as a reservoir. The ontogenic profiles of VEGF, IGF-I and GH in the serum and ocular compartments are specific. These differences should be considered when therapies for ROP are proposed.




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K. D. A. Beharry, H. D. Modanlou, J. Hasan, Z. Gharraee, P. Abad-Santos, J. H. Sills, A. Jan, S. Nageotte, and J. V. Aranda
Comparative Effects of Early Postnatal Ibuprofen and Indomethacin on VEGF, IGF-I, and GH during Rat Ocular Development.
Invest. Ophthalmol. Vis. Sci., July 1, 2006; 47(7): 3036 - 3043.
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