Abstract
Background/Aims: VEGF is an angiogenic factor involved in retinal development through interaction with VEGFR1 and VEGFR2. Neuropilin (Npn) has been shown to enhance VEGF164 affinity for VEGFR2. Pigment epithelium-derived factor (PEDF) is an angiogenic antagonist that is upregulated after retinal vascularization is complete. IB and IN have been shown to improve oxygen-induced retinopathy in mice. We hypothesized that IB is more effective than IN for suppression of retinal VEGF signaling in rats.
Methods: Newborn rats (n=3 litters/groups; 15 pups/litter) received IP injections of either saline (Sal), IB (10 mg/Kg), IB (50 mg/Kg), IN (0.2 mg/Kg), or IN (1.0 mg/Kg) on days 1, 2 and 3 postnatal age. At P14, the pups were sacrificed and retinal mRNA expression of VEGF188, VEGF164, VEGF120, VEGFR1, VEGFR2, Npn1, Npn2 and PEDF were examined.
Results: Transcripts for VEGF164 were more abundant in the rat retina than VEGF188 and VEGF120. While no differences in VEGF188 mRNA expression were detected among the groups, VEGF164 transcripts were decreased with 50 mg IB (p<0.05 vs Sal), and both doses of IN (p<0.01 vs Sal). VEGF120 was suppressed only with 50 mg IB (p<0.01 vs Sal). Transcripts for Npn1 and Npn2 were co-expressed and abundant in the retina. Npn1 mRNA remained unchanged but Npn2 mRNA was significantly increased with 1.0 mg IN (p<0.01 vs Sal). IB and IN had no significant effects on retinal VEGFR1 or PEDF mRNA expression.
Conclusions: Abundant expression of Npn1 and Npn2 in the retina suggests their involvement in retinal development. Although IN suppressed retinal VEGF164 transcripts, it had no effect on VEGFR1 and VEGFR2. In contrast, the high dose of IB suppressed VEGF164, VEGF120, and VEGFR2. IB appears to be more effective than IN for suppression of retinal VEGF signaling in rats, suggesting a possible novel therapy for retinal neovascularization.
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Beharry, K., Hasan, J., Aranda, J. et al. 26 Comparative Effects of Ibuprofen (IB) and Indomethacin (IN) for Suppression of Retinal VEGF Signaling in Rats. Pediatr Res 58, 358 (2005). https://doi.org/10.1203/00006450-200508000-00055
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DOI: https://doi.org/10.1203/00006450-200508000-00055
