380 Dietary Arg-Gln Dipeptide or Dha Reduces Pathological Neovascularization (NV) and Promotes Retinal Vessel Re-Growth (VR) in Mouse Model of Rop

Abstract

Aims: ROP is the leading cause of blindness in children. The most abundant sphingolipid in retinal membranes, sphingomyelin (S), is converted to ceramide (C) by acid sphingomyelinase; C/S ratio indicates inflammation and retinal injury. We compared the effects of Arg-Gln dipeptide, alone or with DHA on NV, VR and C/S ratio in a model of ROP.Methods: 7-day old pups and their nursing dams were placed in 75% oxygen for five days. Pups were returned to room air on postnatal day 12 (P12) and supplemented by oral gavage twice daily with Arg- Gln (5 g/kg/d), DHA (2.5 g/kg/d), Arg-Gln + DHA, or vehicle through P17. On P17, pups were sacrificed and perfused with FITC-labeled dextran. Retinas were assessed for NV by enumeration of pre-retinal endothelial cells, intra-retinal vascular density (VR) or C/S ratio by MS.Results: Compared to vehicle, pre-retinal NV was reduced by 61% and 51% with Arg-Gln or DHA (p< 0.05 both), with a 69% reduction observed for Arg- Gln + DHA (p< 0.05). All treatments reduced vasoobliteration vs. vehicle (32% vs. 5.2%, p< 0.05). Arg-Gln, alone or with DHA, promoted intra-retinal vascular density (VR) vs. vehicle (73-76% vs. 53%). Arg-Gln returned retinal C/S ratio to that of control.Conclusion: These results demonstrate the dietary supplementation with Arg-Gln, alone or with DHA, reduces pre-retinal NV and promotes VR in a model of ROP, underscoring the importance of nutrition in modulating disease course. In addition, C/S ratio was normalized by Arg-Gln, supporting a key role for Arg-Gln in reducing acid sphingomyelinase.