Nutrient Supplementation with n3 Polyunsaturated Fatty Acids, Lutein, and Zeaxanthin Decrease A2E Accumulation and VEGF Expression in the Retinas of Ccl2/Cx3cr1-Deficient Mice on Crb1 Background1–3

Ramkumar, Hema L.; Tuo, Jingsheng; Shen, De Fen; Zhang, Jun; Cao, Xiaoguang; Chew, Emily Y.; Chan, Chi‐Chao

doi:10.3945/jn.112.169649

Cited by 58 publications

(51 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lutein and zeaxanthin, which are naturally present in the human macula, decreased A2E levels in RPE of Japanese quails after 16 weeks of supplementation [36]. Ramkumar et al showed that Ccl2 -/- Cx3cr1 -/ - mice fed for 3 months with AREDS2 formula containing lutein and zeaxanthin had lower concentrations of A2E compared to the non-supplemented group [85]. How lutein and zeaxanthin, as well as norbixin, are able to reduce the accumulation of A2E in RPE cells remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo

et al. 2016

View full text Add to dashboard Cite

The accumulation of N-retinylidene-N-retinylethanolamine (A2E, a toxic by-product of the visual pigment cycle) in the retinal pigment epithelium (RPE) is a major cause of visual impairment in the elderly. Photooxidation of A2E results in retinal pigment epithelium degeneration followed by that of associated photoreceptors. Present treatments rely on nutrient supplementation with antioxidants. 9’-cis-Norbixin (a natural diapocarotenoid, 97% purity) was prepared from Bixa orellana seeds. It was first evaluated in primary cultures of porcine retinal pigment epithelium cells challenged with A2E and illuminated with blue light, and it provided an improved photo-protection as compared with lutein or zeaxanthin. In Abca4-/- Rdh8-/- mice (a model of dry AMD), intravitreally-injected norbixin maintained the electroretinogram and protected photoreceptors against light damage. In a standard rat blue-light model of photodamage, norbixin was at least equally as active as phenyl-N-tert-butylnitrone, a free radical spin-trap. Chronic experiments performed with Abca4-/- Rdh8-/- mice treated orally for 3 months with norbixin showed a reduced A2E accumulation in the retina. Norbixin appears promising for developing an oral treatment of macular degeneration. A drug candidate (BIO201) with 9’-cis-norbixin as the active principle ingredient is under development, and its potential will be assessed in a forthcoming clinical trial.

show abstract

Section: Discussionmentioning

confidence: 99%

Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In the AMD eye, typical inflammatory cytokines, including IL-6 [33,49,50] , IL-17 [51,52] , IL-1β [53,54] , tumour necrosis factor-α (TNF-α) [53][54][55][56] , and the enzymes MMP-9 [33,57] and NOS-2 [58,59] contribute to the inflammatory cascade, drusen, and CNV.…”

Section: Discussionmentioning

confidence: 99%

Behaviour of CD11b-Positive Cells in an Animal Model of Laser-Induced Choroidal Neovascularisation

Heiduschka

Alex

et al. 2017

Ophthalmologica

View full text Add to dashboard Cite

Background/Aim: Immune cells, e.g. microglial cells of the retina, appear to be involved in pathological processes in neovascular age-related macular degeneration. Therefore, the purpose of this study was to immunohistochemically check the expression of various factors and cytokines by CD11b-positive (CD11b+) immune cells in an animal model of choroidal neovascularisation (CNV). Methods: We used the animal model of laser-induced CNV in mice. Eyes were isolated at 1, 4, 7, and 14 days after laser treatment. Cryosections were prepared and checked immunohistochemically for the presence of different growth factors and cytokines on microglial cells and other immune cells identified by CD11b immunoreactivity. Results: We found that the number of CD11b+ cells at the laser spots increased dramatically 4 days after laser treatment, the majority of them entering the laser spot most probably by migration. CD11b+ cells in the laser spot were positive for a variety of pro-angiogenic factors, such as PDGF-β, FGF-1, FGF-2, and TGF-β₁. They were also positive for some inflammatory cytokines, in particular TNF-α, IL-6, and CXCL1. In non-treated retinas, CD11b+ cells showed almost no immunoreactivity for these proteins. Conclusion: Microglial cells, macrophages, and other CD11b+ cells may promote the neovascularisation in the laser spot and show a moderate inflammatory behaviour. Immunoreactivity for most of these molecules was found to decrease during the time of observation. Modulation of immune cell activity may thus be a tool to reduce the extent of CNV.

show abstract

“…In 2013, Ramkumar et al [25] measured VEGF levels in mice that received the AREDS2 diet with 1.76 μmol of lutein versus mice in a control group; the research team concluded that the group that received lutein had significantly lower levels of VEGF. Indeed, there are some discrepancies in the literature with respect to the ability of lutein to decrease VEGF levels; these discrepancies may be partially attributed to different doses of lutein, different experimental systems, and other factors.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment of RPE Cells with Lutein Can Mitigate Bevacizumab-Induced Increases in Angiogenin and bFGF

Vilà¹,

Coblentz²,

Neto³

et al. 2016

Ophthalmic Res

View full text Add to dashboard Cite

Purpose: To determine whether pretreatment of retinal pigmented epithelial (RPE) cells with lutein can affect the response of cells to bevacizumab therapy. Methods: One human RPE cell line (ARPE-19) was used for all experiments. The cells were treated with lutein in different concentrations (0.01, 0.1, 1, 10, or 100 μg/ml). After 24 h, all plates were treated with bevacizumab (0.25 mg/ml). Media were harvested 24 h later for sandwich ELISA-based angiogenesis arrays. A Quantibody Human Angiogenesis Array was used in order to quantify the secretion of the following 10 proangiogenic cytokines: angiogenin, ANG2, EGF, bFGF, HB-EGF, PDGF-BB, leptin, PIGF, HGF and VEGF. Results: Treatment with bevacizumab alone led to a significant decrease in VEGF, as well as a significant increase in angiogenin and bFGF. Pretreatment with 0.1 and 1.0 μg/ml of lutein led to significant decreases in both bFGF and angiogenin following treatment with bevacizumab compared to bevacizumab treatment alone. Lutein alone did not modify the secretion of proangiogenic cytokines. Conclusions: Pretreatment of human RPE cells in culture with specific doses of lutein prior to bevacizumab treatment mitigated the increase in bFGF and angiogenin caused by bevacizumab monotherapy.

show abstract

Nutrient Supplementation with n3 Polyunsaturated Fatty Acids, Lutein, and Zeaxanthin Decrease A2E Accumulation and VEGF Expression in the Retinas of Ccl2/Cx3cr1-Deficient Mice on Crb1 Background1–3

Cited by 58 publications

References 50 publications

Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo

Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo

Behaviour of CD11b-Positive Cells in an Animal Model of Laser-Induced Choroidal Neovascularisation

Pretreatment of RPE Cells with Lutein Can Mitigate Bevacizumab-Induced Increases in Angiogenin and bFGF

Contact Info

Product

Resources

About