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      Placenta Growth Factor in Eyes with Neovascular Glaucoma Is Decreased after Intravitreal Ranibizumab Injection

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          Abstract

          Purpose

          To evaluate changes in the concentrations of placental growth factor (PlGF) and vascular endothelial growth factor-A (VEGF-A) in aqueous humor of patients with neovascular glaucoma (NVG) before and after an intravitreal injection of ranibizumab (IVR) and to determine the underlying correlation between the levels.

          Methods

          The prospective interventional comparative study involved 20 eyes of 20 patients with surgery-required advanced NVG and 20 control subjects from January 2013 to November 2013. The NVG eyes received the IVR treatment before glaucoma surgery. Aqueous humor was collected at the time of the IVR injection (pre- IVR) and at the time of antiglaucomatous surgery (post-IVR). Aqueous humor was also collected at the time of cataract surgery in normal control. Aqueous humor and plasma VEGF-A and PlGF levels were measured with an enzyme-linked immunosorbent assay methods, respectively.

          Results

          The mean aqueous humor PlGF and VEGF-A concentrations in the pre-IVR eyes were significantly higher than in those of the control subjects (p<0.001), whereas the plasma levels showed no significant difference. There was a statistically significant correlation between the aqueous humor PlGF and the VEGF-A concentration ( r = 0.612, p = 0.003). The mean aqueous humor PlGF in the post-IVR eyes dramatically decreased from 1078.36 ± 755.83 to 177.64 ± 151.73 pg/mL (p<0.001). The VEGF-A level showed a similar trend from 3697.64 ± 2104.47 pg/mL to 183.54 ± 130.35 pg/mL (p<0.001).

          Conclusions

          Aqueous humor concentrations of VEGF-A and PlGF were significantly elevated in the eyes with NVG, and there was a positive correlation between the levels. After an IVR treatment, VEGF-A and PlGF were significantly decreased in NVG eyes.

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          Most cited references17

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          HIF-1: mediator of physiological and pathophysiological responses to hypoxia.

          Gregg L. Semenza (2000)
          All organisms can sense O(2) concentration and respond to hypoxia with adaptive changes in gene expression. The large body size of mammals necessitates the development of multiple complex physiological systems to ensure adequate O(2) delivery to all cells under normal conditions. The transcriptional regulator hypoxia-inducible factor 1 (HIF-1) is an essential mediator of O(2) homeostasis. HIF-1 is required for the establishment of key physiological systems during development and their subsequent utilization in fetal and postnatal life. HIF-1 also appears to play a key role in the pathophysiology of cancer, cardiovascular disease, and chronic lung disease, which represent the major causes of mortality among industrialized societies. Genetic or pharmacological modulation of HIF-1 activity in vivo may represent a novel therapeutic approach to these disorders.
          Article 0 comments Cited 347 times – based on 0 reviews     Review now
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            Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration.

            Napoleone Ferrara, Lisa A Damico, Naveed Shams … (2006)
            Angiogenesis is a key aspect of the wet form of age-related neovascular (AMD), the leading cause of blindness in the elderly population. Substantial evidence indicated that vascular endothelial growth factor (VEGF)-A is a major mediator of angiogenesis and vascular leakage in wet AMD. VEGF-A is the prototype member of a gene family that includes also PlGF, VEGF-B, VEGF-C, VEGF-D and the orf virus-encoded VEGF-E. Several isoforms of VEGF-A can be generated due to alternative mRNA splicing. Various VEGF inhibitors have been clinically developed. Among these, ranibizumab is a high affinity recombinant Fab that neutralizes all isoforms of VEGF-A. The article briefly reviews the biology of VEGF and then focuses on the path that led to clinical development of ranibizumab. The safety and efficacy of ranibizumab in the treatment of neovascular AMD have been evaluated in two large phase III, multicenter, randomized, double-masked, controlled pivotal trials in different neovascular AMD patient populations. Combined, the trial results indicate that ranibizumab results not only in a slowing down of vision loss but also in a significant proportion of patients experiencing a clinically meaningful vision gain. The visual acuity benefit over control was observed regardless of CNV lesion type. Furthermore, the benefit was associated with a low rate of serious adverse events. Ranibizumab represents a novel therapy that, for the first time, appears to have the potential to enable many AMD patients to obtain a meaningful and sustained gain of vision. On June 30 2006, ranibizumab was approved by the US Food and Drug Administration for the treatment of wet AMD.
            Article 0 comments Cited 215 times – based on 0 reviews     Review now
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              The discovery of placenta growth factor and its biological activity.

              S Nevot Falcó (2012)
              Angiogenesis is a complex biological phenomenon crucial for a correct embryonic development and for post-natal growth. In adult life, it is a tightly regulated process confined to the uterus and ovary during the different phases of the menstrual cycle and to the heart and skeletal muscles after prolonged and sustained physical exercise. Conversly, angiogenesis is one of the major pathological changes associated with several complex diseases like cancer, atherosclerosis, arthritis, diabetic retinopathy and age-related macular degeneration. Among the several molecular players involved in angiogenesis, some members of VEGF family, VEGF-A, VEGF-B and placenta growth factor (PlGF), and the related receptors VEGF receptor 1 (VEGFR-1, also known as Flt-1) and VEGF receptor 2 (VEGFR-2, also known as Flk-1 in mice and KDR in human) have a decisive role. In this review, we describe the discovery and molecular characteristics of PlGF, and discuss the biological role of this growth factor in physiological and pathological conditions.
              Article 0 comments Cited 129 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                N.S. Duesbery: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 19 January 2016
                Publication date Collection: 2016
                Volume: 11
                Issue: 1
                Electronic Location Identifier: e0146993
                Affiliations
                [1 ]Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, People’s Republic of China
                [2 ]Department of Ophthalmology, Shanghai First People’s Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China
                [3 ]Shanghai Key Laboratory of Fundus Disease, Shanghai, China
                Van Andel Research Institute, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MWZ XLZ. Performed the experiments: MWZ WW JWW WBH XYD. Analyzed the data: MWZ WW. Contributed reagents/materials/analysis tools: WW WBH XYD. Wrote the paper: MWZ.

                Article
                Publisher ID: PONE-D-14-41247
                DOI: 10.1371/journal.pone.0146993
                PMC ID: 4718677
                PubMed ID: 26785251
                SO-VID: 277b06df-fb6e-42df-8862-39b9dd0f432f
                Copyright © © 2016 Zhou et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 15 October 2014
                Date accepted : 28 December 2015
                Page count
                Figures: 5, Tables: 5, Pages: 13
                Funding
                This research was supported by the National Natural Science Foundation of China (81170849, 81371008).
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Endocrinology
                Subject: Endocrine Physiology
                Subject: Growth Factors
                Subject: Placental Growth Factor
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Endocrine Physiology
                Subject: Growth Factors
                Subject: Placental Growth Factor
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Endocrine Physiology
                Subject: Growth Factors
                Subject: Placental Growth Factor
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Head
                Subject: Eyes
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Head
                Subject: Eyes
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Ocular System
                Subject: Eyes
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Ocular System
                Subject: Eyes
                Subject: Medicine and Health Sciences
                Subject: Endocrinology
                Subject: Endocrine Disorders
                Subject: Diabetes Mellitus
                Subject: Medicine and Health Sciences
                Subject: Metabolic Disorders
                Subject: Diabetes Mellitus
                Subject: Medicine and Health Sciences
                Subject: Ophthalmology
                Subject: Eye Diseases
                Subject: Glaucoma
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Cardiovascular Physiology
                Subject: Vasculogenesis
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Cardiovascular Physiology
                Subject: Vasculogenesis
                Subject: Biology and Life Sciences
                Subject: Developmental Biology
                Subject: Morphogenesis
                Subject: Vasculogenesis
                Subject: Medicine and Health Sciences
                Subject: Ophthalmology
                Subject: Eye Diseases
                Subject: Medicine and Health Sciences
                Subject: Surgical and Invasive Medical Procedures
                Subject: Medicine and Health Sciences
                Subject: Vascular Medicine
                Subject: Blood Pressure
                Subject: Hypertension
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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