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      Amniotic membrane transplantation for managing dry eye and neurotrophic keratitis

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          Abstract

          Neurotrophic keratitis (NK), a degenerative disease caused by damage to the trigeminal nerve, abolishes both tearing and blinking reflexes, thus causing the most severe forms of dry eye disease (DED). Conversely, the increasing severity of DED also leads to progressive loss of corneal nerve density, potentially resulting in NK. Both diseases manifest the same spectrum of corneal pathologies including inflammation and corneal epithelial keratitis, which can progress into vision-threatening epithelial defect and stromal ulceration. This review summarizes the current literature regarding outcomes following sutured and sutureless cryopreserved amniotic membrane (AM) in treating DED as well as epithelial defects and corneal ulcers due to underlying NK. These studies collectively support the safety and effectiveness of cryopreserved AM in restoring corneal epithelial health, improving visual acuity in eyes with NK and DED, and alleviating symptomatic DED. Future randomized controlled trials are warranted to validate the above findings and determine whether such clinical efficacy lies in promoting corneal nerve regeneration.

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          Most cited references59

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          Corneal nerves in health and disease.

          Corneal nerves are responsible for the sensations of touch, pain, and temperature and play an important role in the blink reflex, wound healing, and tear production and secretion. Corneal nerve dysfunction is a frequent feature of diseases that cause opacities and result in corneal blindness. Corneal opacities rank as the second most frequent cause of blindness. Technological advances in in vivo corneal nerve imaging, such as optical coherence tomography and confocal scanning, have generated new knowledge regarding the phenomenological events that occur during reinnervation of the cornea following disease, injury, or surgery. The recent availability of transgenic neurofluorescent murine models has stimulated the search for molecular modulators of corneal nerve regeneration. New evidence suggests that neuroregenerative and inflammatory pathways in the cornea are intertwined. Evidence-based treatment of neurotrophic corneal diseases includes using neuroregenerative (blood component-based and neurotrophic factors), neuroprotective, and ensconcing (bandage contact lens and amniotic membrane) strategies and avoiding anti-inflammatory therapies, such as cyclosporine and corticosteroids. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas.

            After n-heptanol removal of the total corneal epithelium and a limbal lamellar keratectomy, 23 rabbit eyes developed features of limbal stem cell deficiency including conjunctival epithelial ingrowth, vascularization and chronic inflammation. One month later, 10 control eyes received a total keratectomy, and 13 experimental eyes received additional transplantation of glycerin-preserved human amniotic membrane. In 3 months of follow-up, all control corneas were revascularized to the center with granuloma and retained a conjunctival epithelial phenotype. In contrast, five corneas in the experimental group became clear with either minimal or no vascularization; the rest had either mid peripheral (n = 5) or total (n = 3) vascularization and cloudier stroma. The success of corneal surface reconstruction correlated with the return of a cornea-like epithelial phenotype and the preservation of amniotic membrane, whereas the failure maintained a conjunctival epithelial phenotype and the amniotic membrane was either partially degraded or covered by host fibrovascular stroma. These results suggest that measures taken to facilitate epithelialization without allowing host fibrovascular ingrowth onto the amniotic membrane might prove this procedure clinically useful for ocular surface reconstruction.
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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.

              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.
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                Author and article information

                Journal
                Taiwan J Ophthalmol
                Taiwan J Ophthalmol
                TJO
                Taiwan Journal of Ophthalmology
                Wolters Kluwer - Medknow (India )
                2211-5056
                2211-5072
                Jan-Mar 2020
                04 March 2020
                : 10
                : 1
                : 13-21
                Affiliations
                [1 ] R&D Department, TissueTech Inc., Miami, FL, USA
                [2 ] Department of Ophthalmology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
                [3 ] Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA
                [4 ] Ocular Surface Center, Miami, FL, USA
                Author notes
                [* ] Address for correspondence: Dr. Scheffer C. G. Tseng, Ocular Surface Center, 7235 NW 19th Street Suite C, Miami 33126, FL, USA. E-mail: stseng@ 123456ocularsurface.com
                Article
                TJO-10-13
                10.4103/tjo.tjo_5_20
                7158925
                32309119
                acf545dc-b2ce-4620-b6d4-d3220c154301
                Copyright: © 2020 Taiwan J Ophthalmol

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 25 November 2019
                : 12 January 2020
                Categories
                Review Article

                amniotic membrane,corneal ulcer,dry eye,epithelial defect,neurotrophic keratitis

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