Hypericin inhibits pathological retinal neovascularization in a mouse model of oxygen-induced retinopathy.
OBJECTIVE
Ocular neovascularization is a leading cause of blindness in ischemic retinopathies. Hypericin is an active ingredient in the medical herb St. John's Wort (SJW). Because hypericin inhibits intracellular signaling pathways that are believed to participate in the regulation of angiogenesis, we investigated the actions of hypericin and SJW in retinal neovascularization, using a mouse model of oxygen-induced retinopathy (OIR).


METHODS
C57BL/6 neonatal mice were exposed to a 75% concentration of oxygen from postnatal day 7 (P7) to P12 and returned to room air from P12 to P17 to induce retinal neovascularization. SJW (15 mg/kg/day), hypericin (15, 45, or 135 mug/kg/day), or vehicle was given by gavage once a day for five days from P12 to P17. To quantify the area of retinal neovascularization and vasoobliteration, we stained retinas with isolectin B4 at P17. Phosphorylation of extracellular signal-regulated kinase (ERK) in ischemic retinas was determined by western blot analysis. To estimate retinal vascularization, we stained retinas with isolectin B4 at P7 after treatment with SJW, hypericin, or vehicle from P3 to P7.


RESULTS
Gavage administration of hypericin or SJW significantly inhibited the degree of retinal neovascularization, but did not affect the area of retinal vasoobliteration in a mouse model of OIR. Both SJW and hypericin had no effect on normal vascularization over the treatment time course. Treatment with SJW or hypericin reduced phosphorylation of ERK in the retina.


CONCLUSIONS
These data suggest that hypericin and SJW reduce pathological retinal neovascularization and that administration of these agents could have clinical utility for treatment of ischemic retinopathies.
Higuchi
Akiko
A
Department of Ophthalmology, Kansai Medical University, Osaka, Japan.
Yamada
Haruhiko
H
Yamada
Eri
E
Jo
Nobuo
N
Matsumura
Miyo
M
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000873:Anthracenes; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D020902:Hypericum / Q000378:metabolism; D007511:Ischemia; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010100:Oxygen; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D012160:Retina / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D012164:Retinal Diseases / Q000139:chemically induced / Q000473:pathology*; D015861:Retinal Neovascularization / Q000473:pathology*
D020533:Angiogenesis Inhibitors; D000873:Anthracenes; D010569:Perylene; C004965:hypericin; D048049:Extracellular Signal-Regulated MAP Kinases; D010100:Oxygen