Diabetic retinopathy (DR) develops in a significant proportion of patients with chronic diabetes, characterized by
retinal macular edema and abnormal retinal vessel outgrowth leading to vision loss.
Chrysin, a naturally-occurring
flavonoid found in herb and honeycomb, has anti-inflammatory,
antioxidant, and anti-
cancer properties. This study sought to determine the protective effects of
chrysin on
retinal neovascularization with abnormal vessels and blood-retinal barrier (BRB) breakdown in 33 mM
glucose-exposed human
retinal endothelial cells and in db/db mouse eyes. High
glucose caused
retinal endothelial apoptotic injury, which was inhibited by submicromolar
chrysin. This compound diminished the enhanced induction of HIF-1α,
vascular endothelial growth factor (
VEGF), and
VEGF receptor-2 (VEGFR2) in high
glucose-exposed
retinal endothelial cells. Consistently,
oral administration of 10 mg/kg
chrysin reduced the induction of these
proteins in db/db mouse eye tissues. In addition,
chrysin restored the decrement of
VE-cadherin and ZO-1 junction
proteins and
PECAM-1 in
hyperglycemia-stimulated
retinal endothelial cells and diabetic mouse retina, possibly maintaining tight cell-cell interactions of endothelial cells and pericytes. Anti-apoptotic
chrysin reduced the up-regulation of Ang-1, Ang-2, and Tie-2 crucial to
retinal capillary occlusion and BRB permeability. Furthermore, orally treating
chrysin inhibited acellular capillary formation, neovascularization, and vascular leakage observed in diabetic retinas. These observations demonstrate, for the first time, that
chrysin had a capability to encumber diabetes-associated
retinal neovascularization with microvascular abnormalities and BRB breakdown.