Article Text

SUPPRESSION OF OXYGEN-INDUCED RETINOPATHY WITH JB1 (AN IGF-1 PEPTIDE ANALOGUE) IN NEONATAL RATS
  1. R S Brock1,
  2. K D Beharry1,
  3. B Gebrekristos1,
  4. K Kuniyoshi1,
  5. R J Coleman1,
  6. H D Modanlou1
  1. 1University of California Irvine, Irvine, California, USA

Abstract

Background Insulin-like growth factor type 1 (IGF-1) is a permissive factor for vascular endothelial growth factor (VEGF) in normal and pathological vascular development.

Objective JB1 (an IGF-1 analogue that inhibits the autophosphorylation of the IGF-1 receptor by IGF-1) administration during hyperoxia suppresses oxygen-induced retinopathy (OIR).

Methods Rats at birth (P1) were exposed to 50% with three brief episodes of 12% oxygen every 6 h, for 14 days (P14). They were treated with: (1) JB1 (1 g/day) on P2, P3 and P4 (JB1X3); (2) JB1 on P2, P4, P6, P8, P10, P12, P14 (JB1X7); or (3) saline. Rats were killed at P14 or recovered in room air (RA) until P21. Controls were in RA from birth to P14 or P21. Serum, retina and vitreous fluid were assessed for VEGF and soluble VEGF receptor 1 (VEGFR-1). Retinal vasculature was assessed using fluorescein-dextran and adenosine diphosphatase staining.

Results JB1 had no effects on serum VEGF in RA. In O2, JB1X7 decreased serum VEGF (p<0.05) versus saline at P14. In vitreous fluid VEGF was decreased with JB1X3 in RA (p<0.01 vs saline). Similar reductions were noted in the saline O2 (p<0.05 vs saline RA), but not in the JB1-treated O2 groups. A dose-related increase in serum VEGFR-1 was noted with JB1 in RA (p<0.01 vs saline) and in O2 (p<0.05 vs saline). Vitreous fluid serum VEGFR-1 decreased with JB1X7 in RA (p<0.05 vs saline) and O2 (p<0.001 vs saline). Retinal serum VEGFR-1 decreased in O2, but not JB1. Both JB1 dosing regimens resulted in suppressed retinal neovascularisation at P14 and P21.

Conclusions JB1 may be used to suppress neovascularisation in retinopathy of prematurity.

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