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      Tissue Response to Implanted Ahmed Glaucoma Valve with Adjunctive Amniotic Membrane in Rabbit Eyes

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          Aims: To investigate the histopathology of the fibrous capsule around Ahmed glaucoma valves (AGVs) implanted with adjunctive amniotic membranes in rabbits. Methods: AGV implantation with or without adjunctive amniotic membrane was performed in a single eye of 20 albino rabbits. The upper surface of the AGV body was covered with amniotic membrane in the study group. After 2 months, histology was used to compare the thickness and characteristics of the fibrous capsule, transdifferentiation of myofibroblasts, and density of blood vessels and leukocytes between the study and control groups. Results: The fibrous capsule along the roof of the bleb was composed of compact collagen fibers with minimal vascularization in the control group. In contrast, in the study group, the fibrous capsule was looser and had a more disorganized collagen architecture. The thickness of the fibrous capsule and the myofibroblast layer was significantly thinner in the study group than in the control group (p < 0.001). The number of CD31-positive blood vessels did not differ between the two groups (p = 0.235). CD45-positive inflammatory cells were more frequently observed in the study group than the control group (p = 0.001). The groups did not differ in the thickness of the fibrous capsule or myofibroblast layer, or the density of blood vessels and leukocytes along the floor of the bleb. Conclusions: Adjunctive amniotic membranes could reduce the risk of encapsulation and aqueous outflow resistance by altering the tissue response to implanted AGVs and subsequent formation of a loose thin capsule.

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          Most cited references 24

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          Identification of antiangiogenic and antiinflammatory proteins in human amniotic membrane.

           D. Ma,  S. H. Kim,  Y Hao (2000)
          To identify the potential antiangiogenic and antiinflammatory proteins expressed in human amniotic membrane tissue. Human amniotic epithelial and mesenchymal cells were isolated from human amniotic membranes by sequential trypsin and collagenase digestion. Total RNAs were harvested from freshly obtained human amniotic epithelial and mesenchymal cells. Antiangiogenic and antiinflammatory proteins were detected by the reverse transcriptase-polymerase chain reaction (RT-PCR) technique and further confirmed by DNA sequencing of PCR-amplified transcripts. The distribution of tissue inhibitors of metalloproteinase (TIMPs) were studied further by immunohistochemistry performed on paraffin-embedded amniotic membrane tissue. RT-PCR results showed that both human amniotic epithelial and mesenchymal cells express interleukin-1 receptor antagonist, all four TIMPs, collagen XVIII, and interleukin-10. Thrombospondin-1 was expressed in all of the epithelial cell specimens and in one out of five mesenchymal cell specimens. Furthermore, immunohistochemistry studies performed on freshly prepared amniotic membrane confirmed that all members of the TIMP family were present in epithelial and mesenchymal cells as well as in the compact layer of the amniotic stroma. In cryopreserved amniotic membranes, positive staining was seen in residual amniotic cells and stroma. Human amniotic membrane epithelial and mesenchymal cells express various antiangiogenic and antiinflammatory proteins. Some of those proteins also were found in amniotic membrane stroma. These findings may explain in part the antiangiogenic and antiinflammatory effects of amniotic membrane transplantation.
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            Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation.

            We have examined the role of mechanical tension in myofibroblast differentiation using two in vivo rat models. In the first model, granulation tissue was subjected to an increase in mechanical tension by splinting a full-thickness wound with a plastic frame. Myofibroblast features, such as stress fiber formation, expression of ED-A fibronectin and alpha-smooth muscle actin (alpha-SMA) appeared earlier in splinted than in unsplinted wounds. Myofibroblast marker expression decreased in control wounds starting at 10 days after wounding as expected, but persisted in splinted wounds. In the second model, granuloma pouches were induced by subcutaneous croton oil injection; pouches were either left intact or released from tension by evacuation of the exudate at 14 days. The expression of myofibroblast markers was reduced after tension release in the following sequence: F-actin (2 days), alpha-SMA (3 days), and ED-A fibronectin (5 days); cell density was not affected. In both models, isometric contraction of tissue strips was measured after stimulation with smooth muscle agonists. Contractility correlated always with the level of alpha-SMA expression, being high when granulation tissue had been subjected to tension and low when it had been relaxed. Our results support the assumption that mechanical tension is crucial for myofibroblast modulation and for the maintenance of their contractile activity.
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              Suppression of transforming growth factor-beta isoforms, TGF-beta receptor type II, and myofibroblast differentiation in cultured human corneal and limbal fibroblasts by amniotic membrane matrix.

               X Ma,  Kun Li,  J. Tseng (1999)
              Down-regulation of the transforming growth factor-beta (TGF-beta) signaling system is a strategy for preventing scarring during wound healing. Human corneal and limbal fibroblasts were cultured on the stromal matrix side of preserved human amniotic membrane. The levels of TGF-beta1, beta2, and beta3 and TGF-beta type II receptor transcripts and TGF-beta1 and beta2 proteins were suppressed as early as 8 hr and more dramatically at 24 hr after contact with an amniotic membrane. This suppressive effect was accompanied by down-regulation of alpha-smooth muscle actin, EDA spliced form of fibronectin, and integrin alpha5. It persisted even when challenged by 10 ng/ml TGF-beta1. In contrast with their counterparts grown on plastic or in collagen gel, such suppression in amniotic membrane cultures remained complete after 1 week of culturing. Cells cultured on amniotic membrane showed significantly reduced [3H]-thymidine incorporation compared to cells cultured on plastic and displayed no DNA fragmentation. These results reveal a novel mechanism by which the TGF-beta signaling system, DNA synthesis, and subsequent myofibroblast differentiation can be suppressed by an amnionic membrane matrix. This action explains in part the antiscarring results of amniotic membrane transplantation used for ocular surface reconstruction, a surgical technique applicable to other subspecialties. It may also explain in part why fetal wound healing is scarless.

                Author and article information

                Ophthalmic Res
                Ophthalmic Research
                S. Karger AG
                March 2014
                05 February 2014
                : 51
                : 3
                : 129-139
                aDepartment of Ophthalmology, bMedical Research Institute and cDepartment of Pathology, Pusan National University Hospital, and dDepartment of Ophthalmology, Busan Paik Hospital, Inje University College of Medicine, Busan, and eDepartment of Ophthalmology, Daegu Fatima Hospital, Daegu, Korea
                Author notes
                *Ji Woong Lee, MD, Department of Ophthalmology, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739 (Korea), E-Mail glaucoma@pnu.ac.kr
                357097 Ophthalmic Res 2014;51:129-139
                © 2014 S. Karger AG, Basel

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 12, Tables: 1, Pages: 11
                Original Paper


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