Foredragsholder / Presenter

Navn / Name: Chatarina Löfqvist

Institution: The Sahlgrenska Academy at Göteborg University

Afdeling / Department: Dept of Physiology

E-mail: chatarina.lofqvist@vgregion.se

Medforfattere / Co-authors:

Navn / Name: Kip Connor

Institution: Children's Hospital, Harvard Medical School, Boston

Afdeling / Department: Department of Ophthalmology

Navn / Name: Christopher M. Aderman

Institution: Children's Hospital, Harvard Medical School, Boston

Afdeling / Department: Department of Ophthalmology

Navn / Name: Jing Chen

Children's Hospital, Harvard Medical School, Boston

Afdeling / Department: Department of Ophthalmology

Navn / Name: Ann Hellstrom

The Sahlgrenska Academy at Göteborg University

Afdeling / Department: Dept of Clinical Neurosciences

Navn / Name: Lois EH Smith

Institution: Children's Hospital, Harvard Medical School, Boston

Afdeling / Department: Department of Ophthalmology

ABSTRACT

Increased dietary intake of ω-3 PUFA reduces pathological retinal angiogenesis

We studied the influence of ω-3 and ω-6 long chain polyunsaturated fatty acids (PUFA) on vascular loss, vascular re-growth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy. We show that increasing ω-3 PUFA tissue levels by dietary or genetic means decreases the area of avascular retina by increasing vessel re-growth after injury, thereby reducing the hypoxic stimulus for pathological neovascularization. The bioactive ω-3 PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protect against neovascularization. The protective effect of ω-3 PUFAs and their bioactive metabolites is mediated in part through suppression of TNF-α. This inflammatory cytokine is found in a subset of microglia/macrophages that are closely associated with retinal vessels. These effects on angiogenesis are likely to be important for retinopathy. The results of the present study suggest that enriching the sources of ω-3 PUFA may be an effective therapeutic approach to help prevent proliferative retinopathy. In addition, the resolvins, RvD1 and RvE1, and the neuroprotectin NPD1 are potent anti-inflammatory and pro-resolving mediators. The present study establishes the first results indicating that these novel mediators are also potent regulators of angiogenesis. If supplementing sources of Docosahexaenoic acid ( DHA), Eicosapentaenoic acid ( EPA) or their bioactive mediators, as demonstrated by the present findings, this cost effective intervention could benefit the new generation of preterm born children worldwide.