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271 ONTOGENY OF VASCULAR ENDOTHELIAL GROWTH FACTOR, INSULIN-LIKE GROWTH FACTOR-I, AND GROWTH HORMONE IN THE RAT VITREOUS FLUID, RETINAL HOMOGENATES, AND SYSTEMIC CIRCULATION: RELATIONSHIP TO PHYSICAL GROWTH AND RETINAL DEVELOPMENT
  1. Z. Gharraee,
  2. K. D.A. Beharry,
  3. J. Hasan,
  4. J. Waltzman,
  5. S. Nageotte,
  6. H. D. Modanlou
  1. University of California Irvine Medical Center, Orange

Abstract

Vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, and growth hormone (GH) are important regulators of physical growth and have been shown to play key roles in retinal angiogenesis and development. In premature infants, low serum IGF-I and high GH levels in the early postnatal period were reported to be associated with severe retinopathy of prematurity (ROP). We examined the ontogenic profile of VEGF, IGF-I and GH in rat vitreous fluid, retinal homogenates and systemic circulation from birth to 21 days postnatal age (weaning, P21). Sprague Dawley rats (litter size =15 pups) were sacrificed at P0, P7, P14 and P21 (3 litters/group). At sacrifice, the pups were weighed and measured for linear growth (nose to tail length). Vitreous fluid, retinal homogenates, and serum were analyzed for VEGF, IGF-I and GH by enzyme immunoassay. VEGF levels were 10-fold higher in the vitreous (pg/mL) than serum (pg/mL) at all stages of development. Vitreous and serum VEGF levels progressively declined at P7, P14 and P21 (p≤0.05 to p≤0.001) compared to term, however in the retinal homogenates, VEGF levels (pg/mg protein) increased with the highest concentration at P21 (p≤0.05 vs term). Vitreous IGF-I levels were decreased at P7 through P14 (p≤0.05) compared to term. Vitreous GH levels were 10-fold lower than serum levels and were decreased at P14 and P21 (p≤0.001) compared to P7. Despite a trend for increasing IGF-I and decreasing GH in retinal homogenates, no appreciable changes were detected with advancing postnatal age. Similarly, serum IGF-I levels increased with postnatal age (P14 and P21: p≤0.05 vs term), whereas serum GH levels were decreased at P7 (p≤0.05), P14 (p≤0.01), and P21 (p≤0.01) compared to term. In rats, retinal development occurs postnatally by P14. Our data demonstrate that during normal retinal development, VEGF, IGF-I and GH decrease in the vitreous; and VEGF and IGF-I increase, while GH decreases in the retinal homogenates. A quite different ontogenic pattern is noted in the systemic circulation. VEGF and GH decrease, while IGF-I increases with advancing physical growth. We therefore conclude that any future therapy for ROP should consider changes occurring in the eye rather than the systemic compartment.

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