scholarly journals Salvianolic Acid A Inhibits OX-LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Ke Mao ◽  
Wanting Shu ◽  
Libin Liu ◽  
Qing Gu ◽  
Qinghua Qiu ◽  
...  
Keyword(s):  
Choroidal Neovascularization ◽  
Vascular Diseases ◽  
Age Related Macular Degeneration ◽  
Cell Junction ◽  
Fundus Fluorescein Angiography ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Age Related ◽  
Angiogenic Proteins

Backgrounds. Age-related macular degeneration is closely related to lipid oxidation, while relationship between OX-LDL and choroidal neovascularization is unclear. Recently, cylindromatosis is proved to regulate angiogenesis. However, its role in CNV progression remained unclear. Salvianolic acid A is widely used in vascular diseases. We investigated the relationship between OX-LDL and CNV and explore antineovascularization mechanism of Sal A. Methods. C57BL6/J mice were randomized into four groups and injected with PBS or OX-LDL, together with Sal A for one week. CNV was induced by laser; CNV severity was analyzed by fundus fluorescein angiography, H&E staining, and choroid flat mount after 1 week. In in vitro experiments, ARPE-19 and HUVECs were cultured with OX-LDL (with or without Sal A) for 48 hours. Angiogenic proteins, cell junction integrity, and tube formation were measured. CYLD siRNA and specific inhibitors were used to explore mechanisms of CYLD in promoting OX-LDL-induced CNV progression. Results. OX-LDL promoted laser-induced CNV volume by increasing VEGF, PDGF, and CYLD levels. Sal A antagonized OX-LDL effects and restrained CNV progression by decreasing VEGF/PDGF/CYLD, increasing antiangiostatin levels, and promoting P62-CYLD-TRAF6 interaction. Conclusions. We demonstrated oxidation damage exacerbates CNV progression, and Sal A could be a clinical therapeutic reagent to exudative AMD.

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 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.

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

2018 ◽  
Vol 19 (10) ◽  
pp. 2993 ◽  
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 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, migration of endothelial cells, and vascular sprouting from rat aortic ring explants. In a 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 10 μg and 20 μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10 μg/mL and 20 μg/mL of CAD27 instilled, respectively). Retinal function was unaffected, as measured using electroretinography in both groups receiving interareal injection or topical applications of CAD27 for at least fourteen days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in diseases such as neovascular age-related macular degeneration.

scholarly journals CasRx-mediated RNA targeting prevents choroidal neovascularization in a mouse model of age-related macular degeneration

2020 ◽  
Vol 7 (5) ◽  
pp. 835-837 ◽  
Author(s):  
Changyang Zhou ◽  
Xinde Hu ◽  
Cheng Tang ◽  
Wenjia Liu ◽  
Shaoran Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macular Degeneration ◽  
Choroidal Neovascularization ◽  
Age Related Macular Degeneration ◽  
Proof Of Concept ◽  
Rna Transcripts ◽  
Age Related ◽  
Rna Targeting

Summary RNA-targeting CRISPR system Cas13 offers an efficient approach for manipulating RNA transcripts in vitro. In this perspective, we provide a proof-of-concept demonstration that Cas13-mediated Vegfa knockdown in vivo could prevent the development of laser-induced CNV in mouse model of Age-related macular degeneration.

scholarly journals Leveraging Nuclear Receptors as Targets for Pathological Ocular Vascular Diseases

2020 ◽  
Vol 21 (8) ◽  
pp. 2889 ◽  
Author(s):  
Pei-Li Yao ◽  
Jeremy Peavey ◽  
Goldis Malek
Keyword(s):  
Nuclear Receptors ◽  
Vascular Diseases ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
In Vitro Assays ◽  
In Vivo Models ◽  
Age Related ◽  
Vessel Growth

Vasculogenesis and angiogenesis are physiological mechanisms occurring throughout the body. Any disruption to the precise balance of blood vessel growth necessary to support healthy tissue, and the inhibition of abnormal vessel sprouting has the potential to negatively impact stages of development and/or healing. Therefore, the identification of key regulators of these vascular processes is critical to identifying therapeutic means by which to target vascular-associated compromises and complications. Nuclear receptors are a family of transcription factors that have been shown to be involved in modulating different aspects of vascular biology in many tissues systems. Most recently, the role of nuclear receptors in ocular biology and vasculopathies has garnered interest. Herein, we review studies that have used in vitro assays and in vivo models to investigate nuclear receptor-driven pathways in two ocular vascular diseases associated with blindness, wet or exudative age-related macular degeneration, and proliferative diabetic retinopathy. The potential therapeutic targeting of nuclear receptors for ocular diseases is also discussed.

scholarly journals Optical Coherence Tomography Angiography in Retinal Vascular Diseases and Choroidal Neovascularization

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Rodolfo Mastropasqua ◽  
Luca Di Antonio ◽  
Silvio Di Staso ◽  
Luca Agnifili ◽  
Angela Di Gregorio ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Choroidal Neovascularization ◽  
Healthy Subjects ◽  
Optical Coherence Tomography Angiography ◽  
Vascular Diseases ◽  
Age Related Macular Degeneration ◽  
Foveal Avascular Zone ◽  
Optical Coherence ◽  
Age Related ◽  
Split Spectrum

Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A) to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV) in retinal vascular diseases.Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA). Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) with Spectralis HRA + OCT (Heidelberg Engineering GmbH) were performed.Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes), age-related macular degeneration related (2), branch retinal vein occlusion (BRVO) (2), and branch retinal artery occlusion (BRAO) (1). OCT-A images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV.Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A.

scholarly journals RGD-Modified Multifunctional Nanoparticles Encapsulating Salvianolic Acid A for Targeted Treatment of Choroidal Neovascularization

2021 ◽  
Author(s):  
Junxiu Zhang ◽  
Jingyi Zhu ◽  
Lingzhou Zhao ◽  
Ke Mao ◽  
Qing Gu ◽  
...  
Keyword(s):  
Choroidal Neovascularization ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Fluorescein Isothiocyanate ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Low Cytotoxicity ◽  
Arginine Glycine Aspartic Acid

Abstract Background: The development of alternative anti-angiogenesis therapy for choroidal neovascularization (CNV) remains a great challenge. Nanoparticle systems have emerged as a new form of drug delivery in ocular diseases. Here, we report the construction and characterization of arginine-glycine-aspartic acid (RGD)-conjugated polyethyleneimine (PEI) as a vehicle to load antioxidant salvianolic acid A (SAA) for targeted anti-angiogenesis therapy of CNV. In this study, PEI was consecutively modified with polyethylene glycol (PEG) conjugated RGD segments, 3-(4’-hydroxyphenyl) propionic acid-Osu (HPAO), and fluorescein isothiocyanate (FI), followed by acetylation of the remaining PEI surface amines to generate the multifunctional PEI vehicle PEI.NHAc-FI-HPAO-(PEG-RGD) (for short, RGD-PEI). The formed RGD-PEI was utilized as an effective vehicle platform to load SAA. Results: We showed that RGD-PEI/SAA complexes displayed desirable water dispersibility, low cytotoxicity, and sustainable release of SAA under different pH conditions. It could be specifically taken up by ɑvβ5 integrin receptors expressing retinal pigment epithelium (RPE) cells in vitro and selectively accumulated in CNV lesions in vivo. Moreover, the complexes displayed specific therapeutic efficacy in a mouse model of laser induced CNV, and the slow elimination of the complexes in the vitreous cavity was verified by SPECT imaging after 131I radiolabeling. The histological examinations further confimed the biocompatibility of RGD-PEI/SAA.Conclusions: The results suggest that the designed RGD-PEI/SAA complexes may be a potential alternative anti-angiogenesis therapy for posterior ocular neovascular diseases.

scholarly journals PGE2 Promotes Neovascularization and M2 Macrophage Recruitment in Murine Wet-Type AMD Models

2021 ◽  
Author(s):  
Xiaolu Wang ◽  
Pengfei Zhan ◽  
Yuqing Cui ◽  
Yujuan Cao ◽  
Xun Bao ◽  
...  
Keyword(s):  
Interleukin 10 ◽  
Age Related Macular Degeneration ◽  
Prostaglandin E ◽  
M2 Macrophage ◽  
Fundus Fluorescein Angiography ◽  
Macrophage Recruitment ◽  
M2 Polarization ◽  
Age Related ◽  
Wet Amd

Abstract Age-related macular degeneration (AMD), a progressive chronic disease of the central retina, is a leading cause of blindness worldwide. Activated macrophages recruited to the injured eyes greatly contribute to the pathogenesis of choroidal neovascularization (CNV) in exudative AMD (wet AMD). This study describes the effects of cyclooxygenase-2 (COX2)/prostaglandin E2 (PGE2) signalling on the M2 macrophage recruitment and CNV formation of wet AMD. In a mouse model of laser-induced wet AMD, the mice received an intravitreal injection of celecoxib (a selective COX2 inhibitor). Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), choroidal histology of the CNV lesions, and biochemical markers were assessed. The level of PGE2 expression was high in the laser-induced CNV lesions. M2 polarization and CNV development were significantly less after celecoxib treatment. E-prostanoid1 receptor (EP1R)/protein kinase C (PKC) signalling was involved in M2 polarization and interleukin-10 (IL-10) production of bone marrow-derived macrophages (BMDMs) in vitro. In addition, IL-10 was found to induce the proliferation and migration of human choroidal microvascular endothelial cells (HCECs). Thus, the PGE2/EP1R signalling network serves as a potential therapeutic target for CNV of the wet-type AMD.

scholarly journals A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of Choroidal Neovascularization

2020 ◽  
Vol 21 (8) ◽  
pp. 2689 ◽  
Author(s):  
Christina Kiel ◽  
Patricia Berber ◽  
Marcus Karlstetter ◽  
Alexander Aslanidis ◽  
Tobias Strunz ◽  
...  
Keyword(s):  
Mouse Model ◽  
Choroidal Neovascularization ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
In Vitro Assays ◽  
Subretinal Space ◽  
Circulating Microrna ◽  
Age Related

Choroidal neovascularization (CNV) is a pathological process in which aberrant blood vessels invade the subretinal space of the mammalian eye. It is a characteristic feature of the prevalent neovascular age-related macular degeneration (nAMD). Circulating microRNAs (cmiRNAs) are regarded as potentially valuable biomarkers for various age-related diseases, including nAMD. Here, we investigated cmiRNA expression in an established laser-induced CNV mouse model. Upon CNV induction in C57Bl/6 mice, blood-derived cmiRNAs were initially determined globally by RNA next generation sequencing, and the most strongly dysregulated cmiRNAs were independently replicated by quantitative reverse transcription PCR (RT-qPCR) in blood, retinal, and retinal pigment epithelium (RPE)/choroidal tissue. Our findings suggest that two miRNAs, mmu-mir-486a-5p and mmur-mir-92a-3p, are consistently dysregulated during CNV formation. Furthermore, in functional in vitro assays, a significant impact of mmu-mir-486a-5p and mmu-mir-92a-3p on murine microglial cell viability was observed, while mmu-mir-92a-3p also showed an impact on microglial mobility. Taken together, we report a robust dysregulation of two miRNAs in blood and RPE/choroid after laser-induced initiation of CNV lesions in mice, highlighting their potential role in pathology and eventual therapy of CNV-associated complications.

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