Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice

Abstract

PurposeTo investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms.MethodsC57BL/6N mice were pretreated with intraperitoneal injections of curcumin daily for 3 days prior to laser-induced CNV, and the drug treatments were continued until the end of the study. The CNV area was analyzed by fluorescein-labeled dextran angiography of retinal pigment epithelium (RPE)-choroid flat mounts on day 7 and 14, and CNV leakage was evaluated by fluorescein angiography (FA) on day 14 after laser photocoagulation. The infiltration of F4/80 positive macrophages and GR-1 positive granulocytes were evaluated by immunohistochemistry on RPE-choroid flat mounts on day 3. Their expression in RPE-choroid complex was quantified by real-time PCR (F4/80) and Western blotting (GR-1) on day 3. RPE-choroid levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 were examined by ELISA on day 3. Double immunostaining of F4/80 and VEGF was performed on cryo-sections of CNV lesions on day 3. The expression of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)−1α in the RPE-choroid was determined by Western blotting.ResultsCurcumin-treated mice had significantly less CNV area (P<0.05) and CNV leakage (P<0.001) than vehicle-treated mice. Curcumin treatment led to significant inhibition of F4/80 positive macrophages (P<0.05) and GR-1 positive granulocytes infiltration (P<0.05). VEGF mainly expressed in F4/80 positive macrophages in laser injury sites, which was suppressed by curcumin treatment (P<0.01). Curcumin inhibited the RPE-choroid levels of TNF-α (P<0.05), MCP-1 (P<0.05) and ICAM-1 (P<0.05), and suppressed the activation of NF-κB in nuclear extracts (P<0.05) and the activation of HIF−1α (P<0.05).ConclusionCurcumin treatment led to the suppression of CNV development together with inflammatory and angiogenic processes including NF-κB and HIF−1α activation, the up-regulation of inflammatory and angiogenic cytokines, and infiltrating macrophages and granulocytes. This provides molecular and cellular evidence of the validity of curcumin supplementation as a therapeutic strategy for the suppression of age-related macular degeneration (AMD)-associated CNV.

Knockout of Ccr2 alleviates photoreceptor cell death in rodent retina exposed to chronic blue light

“…23, 24 Of note, microglia have a controversial role in light-induced retinopathy. Although others suggested that microglia could remove apoptotic photoreceptors and cell debris in the injured retina and benefit photoreceptor survival, 25, 26 our work 27, 28 and other groups 29, 30 indicated excessive recruitment and activation of microglia could precede photoreceptor degeneration and was associated with proinflammatory and neurotoxic cytokines in the affected regions. A noteworthy fact is that no study has so far focused on the controversial role of microglia in chronic light-induced retinopathy.…”

The effects of anti‐VEGF and kinin B1 receptor blockade on retinal inflammation in laser‐induced choroidal neovascularization

“…These chemokines, by participating in the recruitment of macrophages, spread the degeneration to the retina (Rutar & Provis, ). The overexpression of TNF‐α, VEGF, and IL‐1β along with increased density of macrophages has been shown in excised choroidal neovascular membranes of AMD patients, as well as in laser‐induced CNV (Grossniklaus et al, ; Sheridan et al, ; Xie et al, ; Zou, Xu, & Chiou, ). These molecules may promote angiogenesis (Lavalette et al, ; Yang, Wang, Qian, Zhang, & Huang, ) and vascular hyperpermeability (Clermont et al, ).…”

Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice

“…Although the drug-delivery of curcumin is mostly gavage [25], oral [60], or by intraperitoneal injection [61], and rarely by intravitreal injection [31], we chose intravitreal injection to achieve the effective local concentration rapidly. In addition, intravitreal injection can be used to distinguish between the treated and untreated eye of a mouse [62-66].…”