scholarly journals Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization

2017 ◽  
Vol 114 (36) ◽  
pp. E7545-E7553 ◽  
Author(s):  
Eiichi Hasegawa ◽  
Saori Inafuku ◽  
Lama Mulki ◽  
Yoko Okunuki ◽  
Ryoji Yanai ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Choroidal Neovascularization ◽  
Vascular Function ◽  
Vision Loss ◽  
Second Messengers ◽  
Age Related Macular Degeneration ◽  
P450 Monooxygenase ◽  
Genetic Ablation ◽  
Age Related ◽  
Lipid Metabolites

Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A growing body of evidence supports a strong link between neovascular disease and inflammation. Metabolites of long-chain polyunsaturated fatty acids derived from the cytochrome P450 (CYP) monooxygenase pathway serve as vital second messengers that regulate a number of hormones and growth factors involved in inflammation and vascular function. Using transgenic mice with altered CYP lipid biosynthetic pathways in a mouse model of laser-induced CNV, we characterized the role of these lipid metabolites in regulating neovascular disease. We discovered that the CYP-derived lipid metabolites epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs) are vital in dampening CNV severity. Specifically, overexpression of the monooxygenase CYP2C8 or genetic ablation or inhibition of the soluble epoxide hydrolase (sEH) enzyme led to increased levels of EDP and EEQ with attenuated CNV development. In contrast, when we promoted the degradation of these CYP-derived metabolites by transgenic overexpression of sEH, the protective effect against CNV was lost. We found that these molecules work in part through their ability to regulate the expression of key leukocyte adhesion molecules, on both leukocytes and endothelial cells, thereby mediating leukocyte recruitment. These results suggest that CYP lipid signaling molecules and their regulators are potential therapeutic targets in neovascular diseases.

The Effects of Indocyanine Green Dye-Enhanced Photocoagulation on the Blood Flow in the Choriocapillaris and the Choroidal Neovascularization (CNV)

2000 ◽  
Author(s):  
C. von Kerczek ◽  
L. Zhu ◽  
A. Ernest ◽  
C. Eggleton ◽  
L. D. T. Topoleski ◽  
...  
Keyword(s):  
Laser Treatment ◽  
Choroidal Neovascularization ◽  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The United States ◽  
Age Related Macular Degeneration ◽  
Central Vision ◽  
Age Related ◽  
Direct Laser

Abstract Age-related macular degeneration (AMD) is the most common cause of vision loss in patients aged 65 years and older in the United States. In the majority of cases, the loss of central vision is secondary to exudative changes and fibrovascular scarring following choroidal neovascularization (CNV). Prompt laser treatment is recommended [Asrani et al., 1996; Macular Photocoagulation Study Group, 1993; Schneider et al, 1998]. However, direct laser treatment to the entire subfoveal lesion is almost invariably associated with immediate loss of central vision. Loss of central vision may be due to direct damage to foveal photoreceptors and retinal pigment epithelium or from damage to the nerve fiber layer serving foveal function [Han et al., 1988].

scholarly journals Blockade of Platelet-Derived Growth Factor Signaling Inhibits Choroidal Neovascularization and Subretinal Fibrosis in Mice

2020 ◽  
Vol 9 (7) ◽  
pp. 2242
Author(s):  
Ye Liu ◽  
Kousuke Noda ◽  
Miyuki Murata ◽  
Di Wu ◽  
Atsuhiro Kanda ◽  
...  
Keyword(s):  
Growth Factor ◽  
Choroidal Neovascularization ◽  
Vision Loss ◽  
Growth Factor Receptor ◽  
Neutralizing Antibody ◽  
Age Related Macular Degeneration ◽  
Platelet Derived Growth Factor ◽  
Growth Factor Signaling ◽  
Age Related ◽  
Subretinal Fibrosis

Neovascular age related macular degeneration (nAMD) leads to severe vision loss worldwide and is characterized by the formation of choroidal neovascularization (CNV) and fibrosis. In the current study, we aimed to investigate the effect of blockade for platelet derived growth factor receptor-β (PDGFR-β) on the formation of choroidal neovascularization and fibrosis in the laser-induced CNV model in mice. Firstly, the presence of PDGFR-β in CNV lesions were confirmed. Intravitreal injection of PDGFR-β neutralizing antibody significantly reduced the size of CNV and subretinal fibrosis. Additionally, subretinal hyperreflective material (SHRM), a landmark feature on OCT as a risk factor for subretinal fibrosis formation in nAMD patients was also suppressed by PDGFR-β blockade. Furthermore, pericytes were abundantly recruited to the CNV lesions during CNV formation, however, blockade of PDGFR-β significantly reduced pericyte recruitment. In addition, PDGF-BB stimulation increased the migration of the rat retinal pericyte cell line, R-rPCT1, which was abrogated by the neutralization of PDGFR-β. These results indicate that blockade of PDGFR-β attenuates laser-induced CNV and fibrosis through the inhibition of pericyte migration.

scholarly journals The Histone Deacetylase Inhibitor AN7, Attenuates Choroidal Neovascularization in a Mouse Model

2019 ◽  
Vol 20 (3) ◽  
pp. 714
Author(s):  
Mor Dahbash ◽  
Ruti Sella ◽  
Elinor Megiddo-Barnir ◽  
Yael Nisgav ◽  
Nataly Tarasenko ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mouse Model ◽  
Histone Deacetylase ◽  
Choroidal Neovascularization ◽  
Histone Deacetylase Inhibitor ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Age Related ◽  
Deacetylase Inhibitor

: Choroidal neovascularization (CNV) is a complication of age-related macular degeneration and a major contributing factor to vision loss. In this paper, we show that in a mouse model of laser-induced CNV, systemic administration of Butyroyloxymethyl-diethyl phosphate (AN7), a histone deacetylase inhibitor (HDACi), significantly reduced CNV area and vascular leakage, as measured by choroidal flatmounts and fluorescein angiography. CNV area reduction by systemic AN7 treatment was similar to that achieved by intravitreal bevacizumab treatment. The expression of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF-2), and the endothelial cells marker CD31, was lower in the AN7 treated group in comparison to the control group at the laser lesion site. In vitro, AN7 facilitated retinal pigmented epithelium (RPE) cells tight junctions’ integrity during hypoxia, by protecting the hexagonal pattern of ZO-1 protein in the cell borders, hence reducing RPE permeability. In conclusion, systemic AN7 should be further investigated as a possible effective treatment for CNV.

scholarly journals Potential Sources and Roles of Adaptive Immunity in Age-Related Macular Degeneration: Shall We Rename AMD into Autoimmune Macular Disease?

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Serge Camelo
Keyword(s):  
T Cells ◽  
Macular Degeneration ◽  
Retinal Degeneration ◽  
Adaptive Immunity ◽  
Choroidal Neovascularization ◽  
Vision Loss ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Pathologic Features

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly throughout the industrialized world. Its most prominent pathologic features are lesions involving the retinal pigment epithelium (RPE) the Bruch’s membrane, the degeneration of photoreceptors, and, in the most aggressive cases, choroidal neovascularization. Genetic associations between the risk of developing AMD and polymorphism within components of the complement system, as well as chemokine receptors expressed on microglial cells and macrophages, have linked retinal degeneration and choroidal neovascularization to innate immunity (inflammation). In addition to inflammation, players of the adaptive immunity including cytokines, chemokines, antibodies, and T cells have been detected in animal models of AMD and in patients suffering from this pathology. These observations suggest that adaptive immunity might play a role in different processes associated with AMD such as RPE atrophy, neovascularization, and retinal degeneration. To this date however, the exact roles (if any) of autoantibodies and T cells in AMD remain unknown. In this review we discuss the potential effects of adaptive immune responses in AMD pathogenesis.

scholarly journals Inhibition of Experimental Choroidal Neovascularization by a Novel Peptide Derived from Calreticulin Anti-Angiogenic Domain

2018 ◽  
Author(s):  
Youn-Shen Bee ◽  
Yi‐Ling Ma ◽  
Jinying Chen ◽  
Pei-Jhen Tsai ◽  
Shwu-Jiuan Sheu ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Vision Loss ◽  
Aortic Ring ◽  
Age Related Macular Degeneration ◽  
Pathological Feature ◽  
Fundus Fluorescein Angiography ◽  
Age Related ◽  
Topical Applications

Choroidal neovascularization (CNV) is a key pathological feature of several of the leading causes of vision loss including neovascular age-related macular degeneration. Here we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation and migration of endothelial cells, and suppressed vascular sprouting from rat aortic ring explants. In rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10μg and 20μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in the groups of rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10μg/mL and 20μg/mL of CAD27 installed, respectively). Retinal function was unaffected, as measured using electroretinography in both groups received interareal injection or topical applications of CAD27 at least for 9 days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in the diseases such as neovascular age-related macular degeneration.

scholarly journals Optical Coherence Tomography-Angiography of Different Choroidal Neovascularization Subtypes in Wet Age-related Macular Degeneration

Folia Medica ◽  
2019 ◽  
Vol 61 (2) ◽  
pp. 317-326
Author(s):  
Vladimir N. Stavrev ◽  
Nelly P. Sivkova ◽  
Desislava N. Koleva-Georgieva
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Degeneration ◽  
Fluorescein Angiography ◽  
Choroidal Neovascularization ◽  
Optical Coherence Tomography Angiography ◽  
Vision Loss ◽  
Imaging Modality ◽  
Age Related Macular Degeneration ◽  
Optical Coherence ◽  
Age Related

Abstract Age-related macular degeneration is a leading cause of irreversible vision loss in individuals over 55 years of age worldwide. Conventionally, it is divided into two subtypes – dry (non-neovascular) and wet (neovascular) form. Neovascular age-related macular degeneration comprises only 10-15% of all patients but is responsible for more than 80% of blindness related to the disease. It requires early diagnosis and timely treatment. Fluorescein angiography is the current ‘gold standard’ for diagnosing neovascular forms. However, as an invasive procedure, it may be contraindicated in some circumstances and cause serious adverse effects. Optical coherence tomography-angiography is a relatively new, non-invasive and fast imaging modality gaining popularity in the diagnosis of age-related macular degeneration, especially for the neovascular form of the disease. It enables structural and functional information of blood vessels in the retina and choroid, without the need of an intravenous dye. In this study we present and discuss 3 cases of different subtypes of choroidal neovascularization secondary to neovascular age-related macular degeneration. All of them were examined by fluorescein angiography and optical coherence tomography-angiography. The results were qualitatively analyzed.

Ranibizumab for Neovascular Age-Related Macular Degeneration

2020 ◽  
pp. 245-250
Author(s):  
Alan D. Penman ◽  
Kimberly W. Crowder ◽  
William M. Watkins
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Controlled Clinical Trial ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Age Related ◽  
Endothelial Growth Factor

The Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) study was a randomized, double-blind, sham-controlled clinical trial to determine whether intravitreal administration of ranibizumab (an anti-vascular endothelial growth factor [VEGF] agent) prevents vision loss and improves mean visual acuity in patients with minimally classic or occult choroidal neovascularization related to age-related macular degeneration (AMD). Ranibizumab therapy was associated with clinically and statistically significant benefits in visual acuity and the amount of angiographic leakage from choroidal neovascularization during two years of follow-up, with low rates of serious adverse events.

scholarly journals Inhibition of Experimental Choroidal Neovascularization by a Novel Peptide Derived from Calreticulin Anti-Angiogenic Domain

2018 ◽  
Author(s):  
Youn-Shen Bee ◽  
Jinying Chen ◽  
Pei-Jhen Tsai ◽  
Shwu-Jiuan Sheu ◽  
Hsiu-Chen Lin ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Vision Loss ◽  
Aortic Ring ◽  
Age Related Macular Degeneration ◽  
Pathological Feature ◽  
Fundus Fluorescein Angiography ◽  
Age Related ◽  
Topical Applications

Choroidal neovascularization (CNV) is a key pathological feature of several of the leading causes of vision loss including neovascular age-related macular degeneration. Here we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation and migration of endothelial cells, and suppressed vascular sprouting from rat aortic ring explants. In rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10μg and 20μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in the groups of rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10μg/mL and 20μg/mL of CAD27 installed, respectively). Retinal function was unaffected, as measured using electroretinography in both groups received interareal injection or topical applications of CAD27 at least for 9 days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in the diseases such as neovascular age-related macular degeneration.

Progressive Massive Choroidal Neovascularization

2017 ◽  
Vol 1 (3) ◽  
pp. 197-203 ◽  
Author(s):  
Albert Y. Cheung ◽  
Prethy Rao ◽  
Yoshihiro Yonekawa ◽  
Benjamin J. Thomas ◽  
Aparna Shah ◽  
...  
Keyword(s):  
Choroidal Neovascularization ◽  
Vision Loss ◽  
Case Series ◽  
Posterior Pole ◽  
Age Related Macular Degeneration ◽  
Small Subset ◽  
Retrospective Case ◽  
Tertiary Referral Center ◽  
Treatment Regimens ◽  
Age Related

Purpose: A small subset of patients with neovascular age-related macular degeneration (AMD) can have relentless progression of choroidal neovascularization (CNV) and subsequent disciform scarring (DS) with extension beyond the vascular arcades to the equator. We present the clinical courses of this severe phenotype of progressive massive CNV (PM-CNV). Methods: Retrospective case series of 14 eyes of 8 patients who presented with (1) massive DS encompassing the posterior pole and extending to the equator and (2) progressive DS expansion despite treatment between 2004 and 2015 at a tertiary referral center. Demographics, clinical and ocular characteristics, fluorescein angiographic findings, and treatment regimens were reviewed. Results: Baseline characteristics included a mean age of 73.0 years (range, 65.- 86.9 years) with 7 (87.5%) women. Six (75%) patients had bilateral PM-CNV. Mean follow-up was 10.5 years (range, 0.5-18.2 years). Ten (71.4%) eyes underwent intravitreal anti-vascular endothelial growth factor therapy, 3 (21.4%) intravitreal corticosteroid injections, and 3 photodynamic therapy. Most eyes (92.9%) demonstrated subretinal hemorrhage at the edge of the DS prior to DS expansion during treatment. Of the 6 patients with bilateral PM-CNV, 5 developed DS in 1 eye earlier than the subsequent eye (mean time, 63.6 months). Final visual acuity was ≤20/400 in all eyes (20/400 [n = 1]), count fingers (n = 5), hand motions (n = 5), and no light perception (n = 3). Conclusion: Progressive massive CNV is a profound reactivation of DS in some AMD eyes and is associated with severe, often bilateral, vision loss.

scholarly journals Fruquintinib inhibits VEGF/VEGFR2 axis of choroidal endothelial cells and M1-type macrophages to protect against mouse laser-induced choroidal neovascularization

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Xiaojuan Liu ◽  
Aisong Guo ◽  
Yuanyuan Tu ◽  
Wendie Li ◽  
Lele Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Choroidal Neovascularization ◽  
Vision Loss ◽  
Vascular Endothelial Cells ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Age Related ◽  
M1 Polarization

AbstractWet age-related macular degeneration, which is characterized by choroidal neovascularization (CNV) and induces obvious vision loss. Vascular endothelial growth factor (VEGF) family member VEGF-A (also named as VEGF) and its receptor VEGFR2 contribute to the pathogenesis of CNV. Choroidal endothelial cells (CECs) secret C–C motif chemokine ligand 2 (CCL2), which attracts macrophages to CNV lesion and promotes macrophage M1 polarization. Accordingly, infiltrating macrophages secret inflammatory cytokines to promote CNV. In vivo, intravitreal injection of fruquintinib (HMPL-013), an antitumor neovascularization drug, alleviated mouse CNV formation without obvious ocular toxicity. Meanwhile, HMPL-013 inhibited VEGF/VEGFR2 binding in CECs and macrophages, as well as macrophage M1 polarization. In vitro, noncontact coculture of human choroidal vascular endothelial cells (HCVECs) and macrophages under hypoxia conditions was established. HMPL-013 downregulated VEGF/VEGFR2/phosphoinositide-3-kinase/protein kinase B (AKT)/nuclear factor kappa B pathway and CCL2 secretion in HCVECs, as well as VEGF/VEGFR2-induced macrophage M1 polarization under hypoxia condition. In addition, HMPL-013 inhibited HCEVC derived CCL2-induced macrophage migration and M1 polarization, along with macrophage M1 polarization-induced HCVECs proliferation, migration, and tube formation. Altogether, HMPL-013 alleviated CNV formation might via breaking detrimental cross talk between CECs and macrophages.

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