Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos

Sun, Ye; Lin, Zhiqiang; Liu, Chi-Hsiu; Gong, Yan; Liegl, Raffael; Fredrick, Thomas; Meng, Steven; Burnim, Samuel; Wang, Zhongxiao; Akula, James D.; Pu, William T.; Chen, Jing; Smith, Lois E H

doi:10.1084/jem.20161645

Cited by 68 publications

(79 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, mice with Vldlr deficiency developed other pathologic features of wet AMD, such as degeneration of rod and cone photoreceptors and chronic inflammation in the retina and RPE (113,114). The unique pathological features in this mouse model enabled numerous studies that investigated the potential mechanisms and treatments of AMD, RAP, and macular telangiectasia, including antioxidants, neurotrophic factors, resveratrol, anti-inflammation, cellular bioenergetics, and transcriptional control (112,(114)(115)(116)(117)(118)(119), where dietary treatments with either antioxidants or resveratrol were demonstrated to be effective therapies to suppress Vldlr 2/2 neovascularization.…”

Section: Vldlr Germline-knockout Micementioning

confidence: 99%

Animal models of ocular angiogenesis: from development to pathologies

et al. 2017

Self Cite

View full text Add to dashboard Cite

Pathological angiogenesis in the eye is an important feature in the pathophysiology of many vision-threatening diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, as well as corneal diseases with abnormal angiogenesis. Development of reproducible and reliable animal models of ocular angiogenesis has advanced our understanding of both the normal development and the pathobiology of ocular neovascularization. These models have also proven to be valuable experimental tools with which to easily evaluate potential antiangiogenic therapies beyond eye research. This review summarizes the current available animal models of ocular angiogenesis. Models of retinal and choroidal angiogenesis, including oxygen-induced retinopathy, laser-induced choroidal neovascularization, and transgenic mouse models with deficient or spontaneous retinal/choroidal neovascularization, as well as models with induced corneal angiogenesis, are widely used to investigate the molecular and cellular basis of angiogenic mechanisms. Theoretical concepts and experimental protocols of these models are outlined, as well as their advantages and potential limitations, which may help researchers choose the most suitable models for their investigative work.-Liu, C.-H., Wang, Z., Sun, Y., Chen, J. Animal models of ocular angiogenesis: from development to pathologies.

show abstract

Section: Vldlr Germline-knockout Micementioning

confidence: 99%

Animal models of ocular angiogenesis: from development to pathologies

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Dietary modulation of the lipid supply can positively influence diseases with pathological neovascularization such as ROP, AMD, and DR in patients and in animal models of retinopathy (Gong et al , ). Photoreceptor energy demands drive vessel growth (Sapieha, ; Joyal et al , , ; Fu et al , ), while photoreceptor‐derived oxidative stress and inflammation lead to retinal vascular damage or regression (Kern & Berkowitz, ; Sun et al , ). Retinal disorders such as ROP, DR, AMD, RP, and Zellweger spectrum disorder (ZSSD) are associated with disturbances in photoreceptor activity, which may further affect the blood supply and induce pathological vascular remodeling during disease progression.…”

Section: Dyslipidemia In Neurovascular Retinopathiesmentioning

confidence: 99%

Dyslipidemia in retinal metabolic disorders

Chen

Cagnone

et al. 2019

EMBO Mol Med

Self Cite

View full text Add to dashboard Cite

The light‐sensitive photoreceptors in the retina are extremely metabolically demanding and have the highest density of mitochondria of any cell in the body. Both physiological and pathological retinal vascular growth and regression are controlled by photoreceptor energy demands. It is critical to understand the energy demands of photoreceptors and fuel sources supplying them to understand neurovascular diseases. Retinas are very rich in lipids, which are continuously recycled as lipid‐rich photoreceptor outer segments are shed and reformed and dietary intake of lipids modulates retinal lipid composition. Lipids (as well as glucose) are fuel substrates for photoreceptor mitochondria. Dyslipidemia contributes to the development and progression of retinal dysfunction in many eye diseases. Here, we review photoreceptor energy demands with a focus on lipid metabolism in retinal neurovascular disorders.

show abstract

“…Chronic inflammation may induce AMD by stimulating the formation of an abnormal vessel structure. Hemamoeba was discovered in choroiditis in the eyes of AMD patients (7). It was identified that auto-antibodies to attack vitreous bodies, retinal pigment epithelium and retinal tissue in AMD patients (11).…”

Section: Role Of Inflammatory Factors In the Effects Of Aflibercept Omentioning

confidence: 99%

“…However, vascular endothelial growth factor A (VEGF-A), a cytokine that promotes angiogenesis and vascular permeability, is one of the most important factors that promotes neovascularization (6). Active forms of VEGF-A have been identified in CNV (7)(8)(9). Anti-VEGF therapies are now becoming the focus of AMD treatment (7).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of inflammatory factors in the effects of aflibercept or ranibizumab treatment for alleviating wet age‑associated macular degeneration

Yuan

2019

Exp Ther Med

View full text Add to dashboard Cite

Aflibercept and ranibizumab are novel drugs for effectively treating wet age-associated macular degeneration (AMD). In the present study, the effect of aflibercept and ranibizumab on wet AMD was compared. A total of 80 AMD patients were intravitreously treated with aflibercept (2.0 mg/dose, 40 participants) or ranibizumab (0.3 mg/dose, 40 participants). The mean visual acuity and central subfield thickness (CTS) were determined at baseline and each follow-up visit (every 4 weeks). ELISA was used to detect the expression of transforming growth factor-β1 (TGF-β1), monocyte chemoattractant protein 1 (MCP-1) and interleukin 6 (IL-6). The primary outcome was the mean change in visual acuity letter score (VAS) and CTS at 1 year. The VAS was markedly improved by 13.1 in the aflibercept group and by 11.0 in the ranibizumab group. In a subgroup of patients with an initial VAS of <69, the mean improvement in the VAS was 17.7 in the aflibercept group and 13.2 in the ranibizumab group (P<0.01). The mean CTS was markedly decreased by 141 in the aflibercept group and by 134 in the ranibizumab group. In the subgroup of patients with an initial VAS of <69, the mean CTS was decreased by 171 in the aflibercept group and by 154 in the ranibizumab group (P<0.01). However, the change of VAS and CTS was similar between the ranibizumab and aflibercept groups when the initial VAS was ≥69. No significant differences in serious adverse events were identified between the aflibercept and ranibizumab groups. The levels of TGF-β1, IL-6 and MCP-1 were decreased by the aflibercept and ranibizumab treatments. The decrease in the levels of the inflammatory factors was more obvious in patients with an initial VAS of <69 in comparison with that in patients with an initial VAS of ≥69. Negative correlations between the levels of TGF-β1, MCP-1 and IL-6 and the mean change of VAS when patients were treated with aflibercept or ranibizumab were identified among all ages. Positive correlations between the levels of TGF-β1, MCP-1 and IL-6 and the mean change of CTS were observed when the initial VAS of the patients was <69. In conclusion, the efficacy of aflibercept in treating patients with AMD was better than that of ranibizumab when the initial VAS of the patients was <69. The inhibition of inflammatory factors may be a secondary effect of aflibercept and ranibizumab treatment. The present study provides a useful reference for the clinical treatment of wet AMD (Chinese Clinical Trial Registry no. ChiCTR1800017782).

show abstract

Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos

Cited by 68 publications

References 66 publications

Animal models of ocular angiogenesis: from development to pathologies

Animal models of ocular angiogenesis: from development to pathologies

Dyslipidemia in retinal metabolic disorders

Role of inflammatory factors in the effects of aflibercept or ranibizumab treatment for alleviating wet age‑associated macular degeneration

Contact Info

Product

Resources

About