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neovascular cornea

Gore Ariel, Horwitz Vered, Cohen Maayan, Gutman Hila, Cohen Liat, Gez Relli, Kadar Tamar, Dachir Shlomit
PURPOSE: To evaluate the efficacy of ziv-aflibercept as a treatment for established corneal neovascularization (NV) and to compare its efficacy to that of bevacizumab following ocular chemical insult of sulfur mustard (SM) in the rabbit model. METHODS: Chemical SM burn was induced in the right eye of NZW rabbits by vapor exposure. Ziv-aflibercept (2 mg) was applied once to neovascularized eyes by subconjunctival injection while subconjunctival bevacizumab (5 mg) was administered twice a week, for 3 weeks...
March 13, 2018: Experimental Eye Research
Kon-Ichi Arai, Tsutomu Yasukawa, Aki Kato, Ayae Kubota, Hideaki Usui, Noriaki Takase, Soichiro Kuwayama, Yuichiro Ogura
AIMS: Anti-vascular endothelial growth factor agents effectively treat age-related macular degeneration and myopic choroidal neovascularization (CNV). Tissue plasminogen activator (tPA), a fibrinolytic compound, is used as an adjuvant to displace submacular hemorrhage and to treat type 2 CNV. The purpose of this study was to investigate in in vitro and in vivo experiments the antiangiogenic impact of tPA itself. METHODS: The impact of tPA on the proliferation of human umbilical vein endothelial cells (HUVECs) was assessed by an XTT assay [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide]...
March 13, 2018: Ophthalmic Research
James A Grogan, Anthony J Connor, Joe M Pitt-Francis, Philip K Maini, Helen M Byrne
The corneal micropocket angiogenesis assay is an experimental protocol for studying vessel network formation, or neovascularization, in vivo. The assay is attractive due to the ease with which the developing vessel network can be observed in the same animal over time. Measurements from the assay have been used in combination with mathematical modeling to gain insights into the mechanisms of angiogenesis. While previous modeling studies have adopted planar domains to represent the assay, the hemispherical shape of the cornea and asymmetric positioning of the angiogenic source can be seen to affect vascular patterning in experimental images...
March 9, 2018: PLoS Computational Biology
Gaoqin Liu, Peirong Lu, Lei Chen, Wenpeng Zhang, Mengjiao Wang, Dan Li, Xueguang Zhang
PURPOSE: Corneal neovascularization (CrNV) arises from many causes including corneal inflammatory, infectious, or traumatic insult, and frequently leads to impaired vision. This study seeks to determine the role of B-cell leukemia/lymphoma 10 (BCL-10) in the development of experimental CrNV. METHODS: Corneas from BCL-10 knockout (KO) mice and wild-type (WT) mice were burned by sodium hydroxide (NaOH) to create the CrNV model and neovascular formation in the corneas was assessed 2 weeks later...
March 8, 2018: Eye
Yi Lu, Phillip W L Tai, Jianzhong Ai, Dominic J Gessler, Qin Su, Xieyi Yao, Qiang Zheng, Phillip D Zamore, Xun Xu, Guangping Gao
Corneal neovascularization (NV) is the major sight-threatening pathology caused by angiogenic stimuli. Current drugs that directly target pro-angiogenic factors to inhibit or reverse the disease require multiple rounds of administration and have limited efficacies. Here, we identify potential anti-angiogenic corneal microRNAs (miRNAs) and demonstrate a framework that employs discovered miRNAs as biotherapies deliverable by recombinant adeno-associated viruses (rAAVs). By querying differentially expressed miRNAs in neovascularized mouse corneas induced by alkali burn, we have revealed 39 miRNAs that are predicted to target more than 5,500 differentially expressed corneal mRNAs...
March 2, 2018: Molecular Therapy. Nucleic Acids
Yi-Chen Sun, Li-Chuan Yang, Fung-Rong Hu, Chung-Tien Lin, Yan-Ming Chen, Wei-Li Chen
OBJECTIVES: In vivo confocal microscopy was used to observe the morphological presentations and anatomical correlations between corneal neovascularization (NV) and intracorneal lipid deposition in a rabbit model of contact lens (CL)-induced lipid keratopathy secondary to corneal NV. METHODS: Rabbits were divided into 3 groups: (1) 8-week normal diet, (2) 8-week high-cholesterol diet, and (3) 4-week normal diet followed by 4-week high-cholesterol diet. Corneal NV was induced by closed-eye CL...
February 27, 2018: Eye & Contact Lens
Xiao-Pei Zhang, Ke-Ran Li, Qing Yu, Mu-Di Yao, Hui-Min Ge, Xiu-Miao Li, Qin Jiang, Jin Yao, Cong Cao
VEGF-induced neovascularization plays a pivotal role in corneal neovascularization (CoNV). The current study investigated the potential effect of ginsenoside Rh2 (GRh2) on neovascularization. In HUVECs, pretreatment with GRh2 largely attenuated VEGF-induced cell proliferation, migration, and vessel-like tube formation in vitro. At the molecular level, GRh2 disrupted VEGF-induced VEGF receptor 2 (VEGFR2)-Grb-2-associated binder 1 (Gab1) association in HUVECs, causing inactivation of downstream AKT and ERK signaling...
February 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Anthony Mukwaya, Anton Lennikov, Maria Xeroudaki, Pierfrancesco Mirabelli, Mieszko Lachota, Lasse Jensen, Beatrice Peebo, Neil Lagali
Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency...
February 14, 2018: Angiogenesis
Kai-Bao Ji, Ling Ling, Qian Zhang, Jing-Jing Chou, Xia-Ling Yang, Zhi-Hong Wang, Li Yin, Shu-Fang Wu, Yi-Feng Yu
Alkali burns of the cornea may lead to permanent visual impairment or complete blindness. In the current study, the role of microRNA 296 (miR-296) was explored in mouse corneal neovascularization induced by alkali burns. An alkali burn model in Balb/c mice was developed to study chemical corneal injuries. The expression of the miR-296 gene was measured by reverse-transcription-quantitative polymerase chain reaction. Fibroblast growth factor 23 (FGF23) protein expression was measured by western blot analysis...
January 2018: Experimental and Therapeutic Medicine
Chao-Cheng Huang, Hsiao-Mei Kuo, Pei-Chang Wu, Shih-Hsuan Cheng, Tzu-Ting Chang, Yi-Chen Chang, Mei-Lang Kung, Deng-Chyang Wu, Jiin-Haur Chuang, Ming-Hong Tai
AIM: Delta-like 1 homolog (DLK1) is a non-canonical ligand of Notch signaling, which plays a pivotal role in vascular development and tumor angiogenesis. This study aimed to elucidate the function and mechanism of DLK1 in angiogenesis. METHODS AND RESULTS: By using in situ hybridization and immunohistochemical studies, expression analysis revealed a unique vascular tropism of DLK1 in vasculature of neuroblastoma and vascular tumors. Thus, it was hypothesized that DLK1 may be cleaved and then bound to endothelial cells, thereby regulating the endothelial function...
January 30, 2018: Angiogenesis
Hua-Tao Xie, Ying-Ying Zhang, Dong-Ling Jiang, Jun Wu, Jia-Song Wang, Ming-Chang Zhang
To evaluate the outcome of amniotic membrane transplantation (AMT) after tumor excision followed by topical interferon alfa-2b (IFNα2b) drops for primary ocular surface squamous neoplasia (OSSN). Twelve eyes of 12 patients with a mean age of 66±10y were included. The average follow-up was 23±10mo. All 12 patients had limbal involvement. Smooth ocular surface and transparent cornea were achieved in all cases. No sign of inflammation, neovascularization, symblepharon or recurrence was noted at the last follow-up...
2018: International Journal of Ophthalmology
Erika Terzuoli, Lucia Morbidelli, Ginevra Nannelli, Antonio Giachetti, Sandra Donnini, Marina Ziche
The identification of components of the kallikrein-kinin system in the vitreous from patients with microvascular retinal diseases suggests that bradykinin (BK) signaling may contribute to pathogenesis of retinal vascular complications. BK receptor 2 (B2R) signaling has been implicated in both pro-inflammatory and pro-angiogenic effects promoted by BK. Here, we investigated the role of BK/B2R signaling in the retinal neovascularization in the oxygen-induced retinopathy (OIR) model. Blockade of B2R signaling by the antagonist fasitibant delayed retinal vascularization in mouse pups, indicating that the retinal endothelium is a target of the BK/B2R system...
January 23, 2018: International Journal of Molecular Sciences
Medi Eslani, Ilham Putra, Xiang Shen, Judy Hamouie, Asha Tadepalli, Khandaker N Anwar, John A Kink, Samaneh Ghassemi, Gaurav Agnihotri, Sofiya Reshetylo, Alireza Mashaghi, Reza Dana, Peiman Hematti, Ali R Djalilian
Macrophages are crucial drivers of inflammatory corneal neovascularization and thus are potential targets for immunomodulatory therapies. We hypothesized that therapeutic use of cornea derived mesenchymal stromal cells (cMSCs) may alter the function of macrophages. We found that cMSCs can modulate the phenotype and angiogenic function of macrophages. In vitro, cMSCs induce apoptosis of macrophages while preferentially promoting a distinct CD14hi CD16hi CD163hi CD206hi immunophenotype that has significantly reduced angiogenic effects based on in vitro angiogenesis assays...
January 17, 2018: Stem Cells
Anton Lennikov, Pierfrancesco Mirabelli, Anthony Mukwaya, Mira Schaupper, Muthukumar Thangavelu, Mieszko Lachota, Zaheer Ali, Lasse Jensen, Neil Lagali
Corneal neovascularization is a sight-threatening condition caused by angiogenesis in the normally avascular cornea. Neovascularization of the cornea is often associated with an inflammatory response, thus targeting VEGF-A alone yields only a limited efficacy. The NF-κB signaling pathway plays important roles in inflammation and angiogenesis. Here, we study consequences of the inhibition of NF-κB activation through selective blockade of the IKK complex IκB kinase β (IKK2) using the compound IMD0354, focusing on the effects of inflammation and pathological angiogenesis in the cornea...
January 13, 2018: Angiogenesis
R R Zong, Y P Zhou, Z G Liu
microRNA-184 (miR-184) is a small, non-coding, endogenic RNA molecule of 22 nucleotides in length. It is a highly conserved sequence throughout many different species. Multiple studies have demonstrated that miR-184 is an important factor in regulating gene expression at the post-transcriptional level. miR-184 plays vital roles in many biological processes, including development and differentiation in many tissues and organs. Meanwhile, the research on the physiological and pathological role of miR-184 in eyes draws more and more attention lately...
December 11, 2017: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
Hyun Soo Lee, Ji Young Kwon, Choun-Ki Joo
In lamellar keratoplasty, the diseased part of a cornea is replaced while the healthy tissue remains. lamellar keratoplasty has the advantage of better graft survival compared to penetrating keratoplasty (PK). We compared the immunological responses to PK and anterior lamellar keratoplasty (ALK) in a murine model. PK or ALK was performed using C57BL/6 donor grafts and BALB/c recipients, and graft opacity was assessed to evaluate graft rejection up to 8 weeks. We evaluated the immunological responses in both groups, which were not clinically considered as graft failure on postoperative day 21...
January 3, 2018: Experimental Eye Research
Hyun Beom Song, Se Yeon Park, Jung Hwa Ko, Jong Woo Park, Chang Ho Yoon, Dong Hyun Kim, Jeong Hun Kim, Mee Kum Kim, Ryang Hwa Lee, Darwin J Prockop, Joo Youn Oh
The cornea is a transparent tissue devoid of blood and lymphatic vessels. However, various inflammatory conditions can cause hemangiogenesis and lymphangiogenesis in the cornea, compromising transparency and visual acuity. Mesenchymal stem/stromal cells (MSCs) have therapeutic potentials in a variety of diseases because of anti-inflammatory properties. Herein, we investigated the effects of MSCs on corneal angiogenesis using a model of suture-induced inflammatory corneal neovascularization. Data demonstrated that an intravenous administration of MSCs suppressed corneal inflammation and neovascularization, inhibiting both hemangiogenesis and lymphangiogenesis...
January 3, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Dimitrios Kalogeropoulos, Aliki Geka, Konstantinos Malamos, Maria Kanari, Chris Kalogeropoulos
BACKGROUND Keratitis caused by herpes simplex virus (HSV) can have detrimental effects on the cornea leading to loss of vision. Modern therapies can contribute to the prevention of anatomical and functional damage. CASE REPORT An 80-year-old male with complicated HSV-1 keratitis of the left eye (confirmed diagnosis after microbiological investigation) presented three months after antiviral treatment with corneal blurring, severe epitheliopathy, thinning of the stroma, and neovascularization. At the time he was referred, the visual acuity of his left eye was very low, as he could only count fingers at a one-foot distance...
December 27, 2017: American Journal of Case Reports
Yong-Kang Zhang, Jing-Ming Li, Li Qin
AIM: To investigate whether curcumin suppressed corneal neovascularization (CNV) formation via inhibiting activation of Wnt/β-catenin pathway. METHODS: Suture-induced CNV was established on Sprague-Dawley (SD) rats. Curcumin were daily administrated by subconjunctival injection. Phosphorylation of low-density lipoprotein receptor-related protein 6 (LRP6) and nuclear accumulation of β-catenin, two indicators of activated Wnt/β-catenin pathway, were determined by Western-blot analysis in subconfluent/proliferating human microvascular endothelial cells (HMEC) and neovascularized corneas...
2017: International Journal of Ophthalmology
Takeshi Arima, Masaaki Uchiyama, Yuichiro Nakano, Shinya Nagasaka, Dedong Kang, Akira Shimizu, Hiroshi Takahashi
We investigated the effect of a peroxisome proliferator-activated receptor alpha (PPARα) agonist ophthalmic solution in wound healing using a rat corneal alkali burn model. After instillation of a selective agonist of PPARα, fenofibrate, onto the burned cornea, PPARα-positive cells were observed in vascular endothelial cells, and there was upregulation of mRNA of PPARα in corneal stroma. Fenofibrate suppressed expression of neutrophils and macrophages during the early phase, and development of neovascularization and myofibroblast generation during the late phase...
December 19, 2017: Scientific Reports
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