Search results for: chorodial neovascularization

Authors: Zhang Zhenzhen

Abstract:

Valproate (VPA) is commonly used in the treatment of bipolar disorder and epilepsy. The mechanism is complicated, including its ability to inhibit histone deacetylases (HDACs). Here, we show that VPA attenuated VEGF gene expression and the morphological changes in choroidal neovascularization (CNV) induced by photocoagulation in retina. C57BL/6 mice were injected subcutaneously at 300mg/kg twice daily with VPA before insult. Vascular endothelial growth factor (VEGF)-A and VEGF-B were examined in the eyes of VPA-treated mice and in human retinal pigment epithelial cell lines (ARPE-19) exposed to VPA. In addition, CNV was induced by photocoagulation in mice injected with VPA, and the volume of CNV was compared by fluorescence-labeled choroidal flat mount. Morphological changes were analyzed on stained histological sections. Western blot analysis was used to determine protein levels of VEGF-A and VEGF-B, and acetylation of histone H3 in each group. VPA injected intraperitoneally attenuated the VEGF-A and VEGF-B expression in the retina, accompanied by the hyperacetylation of retina tissue, indicating that VPA acts directly on retina tissues through acetylation to reduce the expression of VEGF. VPA also attenuated the VEGF-A mRNA expression in the retinal pigment epithelium showed by immunohistochemistry. Moreover, the administration of VPA significantly attenuated photocoagulation-induced CNV in mice. These results demonstrate that VPA attenuated VEGF production in retina associated with choroidal neovascularization possibly via the HDAC inhibition.

Keywords: retina, acetylation, chorodial neovascularization, vascular endothelial growth factor

Procedia PDF Downloads 166

Authors: Mohammed A. Alfayyadh, Halla A. AlAbdulhadi, Mahdi H. Almubarak

Abstract:

Purpose: Eales’ disease is an idiopathic vasculitis that affects the peripheral retina. It is characterized by recurrent vitreous hemorrhage as a complication of retinal neovascularization. It is more prevalent in India and affects young males. Here we present a patient with neovascular glaucoma as a rare first presentation of Eales’ disease. Observations: This is a 24-year-old Indian gentleman, who complained of a sudden decrease in vision in the left eye over less than 24 hours, along with frontal headache and eye pain for the last three weeks. Ocular examination revealed peripheral retinal ischemia in the right eye, very high intraocular pressure, rubeosis iridis, vitreous hemorrhage and extensive retinal ischemia in the left eye, vascular sheathing and neovascularization in both eyes. Purified protein derivative skin test was positive. The patient was managed with anti-glaucoma, intravitreal anti-vascular endothelial growth factor and laser photocoagulation. Systemic steroids and anti-tuberculous therapy were also initiated. Conclusions: Neovascular glaucoma is an infrequent complication of Eales’ disease. However, the lack of early detection of the disease in the early stages might lead to such serious complication.

Keywords: case report, Eales’ disease, mycobacterium tuberculosis, neovascular glaucoma

Procedia PDF Downloads 90

Authors: Whitehead-Clarke T., Beynon V., Banks J., Karanjia R., Mudera V., Windsor A., Kureshi A.

Abstract:

Introduction: Mesh implants are regularly used to help repair both hiatus hernias (HH) and diaphragmatic hernias (DH). In vivo studies are used to test not only mesh safety but increasingly comparative efficacy. Our work examines the field of in vivo mesh testing for HH and DH models to establish current practices and standards. Method: This systematic review was registered with PROSPERO. Medline and Embase databases were searched for relevant in vivo studies. 44 articles were identified and underwent abstract review, where 22 were excluded. 4 further studies were excluded after full text review – leaving 18 to undergo data extraction. Results: Of 18 studies identified, 9 used an in vivo HH model and 9 a DH model. 5 studies undertook mechanical testing on tissue samples – all uniaxial in nature. Testing strip widths ranged from 1-20mm (median 3mm). Testing speeds varied from 1.5-60mm/minute. Upon histology, the most commonly assessed structural and cellular factors were neovascularization and macrophages, respectively (n=9 each). Structural analysis was mostly qualitative, where cellular analysis was equally likely to be quantitative. 11 studies assessed adhesion formation, of which 8 used one of four scoring systems. 8 studies measured mesh shrinkage. Discussion: In vivo studies assessing mesh for HH and DH repair are uncommon. Within this relatively young field, we encourage surgical and materials testing institutions to discuss its standardisation.

Keywords: hiatus, diaphragmatic, hernia, mesh, materials testing, in vivo

Procedia PDF Downloads 187

Authors: Liang Ning, Chung Hau Yin

Abstract:

Angiogenesis is the process of new blood vessel development. It has been recognized as a therapeutic target for blocking cancer growth four decades ago. Vascular sprouting is initiated by pro-angiogenic factors. Vascular endothelial cell growth factor (VEGF) plays a central role in angiogenic initiation, many patients with cancer or ocular neovascularization have been benefited from anti-VEGF therapy. Emerging approaches impacting in the later stages of vessel remodeling and maturation are expected to improve clinical efficacy. TIE receptor as well as the corresponding angiopoietin ligands, were identified as another endothelial cell specific receptor tyrosine kinase signaling system. Much efforts were made to reduce the activity of angiopoietin-TIE receptor axis. Two eudesmane-type sesquiterpenes from laggera alata, namely, 15-dihydrocostic acid and ilicic acid were found with strong anti-angiogenic properties in zebrafish model. Meanwhile, the mRNA expression levels of VEGFR2 and TIE2 pathway related genes were down-regulated in the sesquiterpenes treated zebrafish embryos. Besides, in human umbilical vein endothelial cells (HUVECs), the sesquiterpenes have the ability to inhibit VEGF-induced HUVECs proliferation and migration at non-toxic concentration. Moreover, angiopoietin-2 induced TIE2 phosphorylation was inhibited by the sesquiterpenes, the inhibitory effect was detected in angiopoietin-1 induced HUVECs proliferation as well. Thus, we hypothesized the anti-angiogenic activity of the compounds may via the inhibition of VEGF and TIE2 related pathways. How the compounds come into play as the pathways inhibitors need to be evaluated in the future.

Keywords: Laggera alata, eudesmane-type sesquiterpene, anti-angiogenesis, VEGF, angiopoietin, TIE2

Procedia PDF Downloads 179

Authors: O. Gsib, U. Peirera, C. Egles, S. A. Bencherif

Abstract:

In skin regenerative medicine, one of the critical issues is to produce a three-dimensional scaffold with optimized porosity for dermal fibroblast infiltration and neovascularization, which exhibits high mechanical properties and displays sufficient wound healing characteristics. In this study, we report on the synthesis and characterization of macroporous sequential interpenetrating polymer networks (IPNs) combining skin wound healing properties of fibrin with the excellent physical properties of polyethylene glycol (PEG). Fibrin fibers serve as a provisional biologically active network to promote cell adhesion and proliferation while PEG provides the mechanical stability to maintain the entire 3D construct. After having modified both PEG and Serum Albumin (used for promoting enzymatic degradability) by adding methacrylate residues (PEGDM and SAM, respectively), Fibrin/PEGDM-SAM sequential IPNs were synthesized as follows: Macroporous sponges were first produced from PEGDM-SAM hydrogels by a freeze-drying technique and then rehydrated by adding the fibrin precursors. Environmental Scanning Electron Microscopy (ESEM) and Confocal Laser Scanning Microscopy (CLSM) were used to characterize their microstructure. Human dermal fibroblasts were cultivated during one week in the constructs and different cell culture parameters (viability, morphology, proliferation) were evaluated. Subcutaneous implantations of the scaffolds were conducted on five-week old male nude mice to investigate their biocompatibility in vivo. We successfully synthesized interconnected and macroporous Fibrin/PEGDM-SAM sequential IPNs. The viability of primary dermal fibroblasts was well maintained (above 90%) after 2 days of culture. Cells were able to adhere, spread and proliferate in the scaffolds suggesting the suitable porosity and intrinsic biologic properties of the constructs. The fibrin network adopted a spider web shape that covered partially the pores allowing easier cell infiltration into the macroporous structure. To further characterize the in vitro cell behavior, cell proliferation (EdU incorporation, MTS assay) is being studied. Preliminary histological analysis of animal studies indicated the persistence of hydrogels even after one-month post implantation and confirmed the absence of inflammation response, good biocompatibility and biointegration of our scaffolds within the surrounding tissues. These results suggest that our Fibrin/PEGDM-SAM IPNs could be considered as potential candidates for dermis regenerative medicine. Histological analysis will be completed to further assess scaffold remodeling including de novo extracellular matrix protein synthesis and early stage angiogenesis analysis. Compression measurements will be conducted to investigate the mechanical properties.

Keywords: fibrin, hydrogels for dermal reconstruction, polyethylene glycol, semi-interpenetrating polymer network

Procedia PDF Downloads 202