Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis.
Many sight-threatening diseases have two critical phases, vessel loss followed by hypoxia-driven destructive neovascularization. These diseases include retinopathy of prematurity and diabetic retinopathy, leading causes of blindness in childhood and middle age affecting over 4 million people in the United States. We studied the influence of omega-3- and omega-6-polyunsaturated fatty acids (PUFAs) on vascular loss, vascular regrowth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy. We show that increasing omega-3-PUFA tissue levels by dietary or genetic means decreased the avascular area of the retina by increasing vessel regrowth after injury, thereby reducing the hypoxic stimulus for neovascularization. The bioactive omega-3-PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protected against neovascularization. The protective effect of omega-3-PUFAs and their bioactive metabolites was mediated, in part, through suppression of tumor necrosis factor-alpha. This inflammatory cytokine was found in a subset of microglia that was closely associated with retinal vessels. These findings indicate that increasing the sources of omega-3-PUFA or their bioactive products reduces pathological angiogenesis. Western diets are often deficient in omega-3-PUFA, and premature infants lack the important transfer from the mother to the infant of omega-3-PUFA that normally occurs in the third trimester of pregnancy. Supplementing omega-3-PUFA intake may be of benefit in preventing retinopathy.
Connor
Kip M
KM
Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
SanGiovanni
John Paul
JP
Division of Epidemiology and Clinical Research, National Eye Institute, 10 Center Drive, Bethesda, Maryland 20892, USA.
Lofqvist
Chatarina
C
Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.|Department of Pediatrics, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Aderman
Christopher M
CM
Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Chen
Jing
J
Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Higuchi
Akiko
A
Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Hong
Song
S
Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
Pravda
Elke A
EA
Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Majchrzak
Sharon
S
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, 12420 Parklawn Drive, Rockville, Maryland 20892, USA.
Carper
Deborah
D
Office of the Director, National Eye Institute, 31 Center Drive, Bethesda, Maryland 20892, USA.
Hellstrom
Ann
A
Dept of Clinical Neurosciences, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Kang
Jing X
JX
Department of Medicine, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Chew
Emily Y
EY
Division of Epidemiology and Clinical Research, National Eye Institute, 10 Center Drive, Bethesda, Maryland 20892, USA.
Salem
Norman
N
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, 12420 Parklawn Drive, Rockville, Maryland 20892, USA.
Serhan
Charles N
CN
Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
Smith
Lois E H
LEH
Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
D000818:Animals; D004032:Diet; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D012164:Retinal Diseases / Q000139:chemically induced / Q000188:drug therapy; D012171:Retinal Vessels / Q000187:drug effects*
D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6