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      The Differential Expression of Cytokines and Growth Factors After SMILE Compared With FS-LASIK in Rabbits

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          Abstract

          Purpose

          To investigate the differential expression of cytokines and growth factors in the cornea and aqueous humor after small incision lenticule extraction (SMILE) compared with femtosecond LASIK (FS-LASIK) using rabbit model.

          Methods

          Sixteen eyes of 16 rabbits in each group underwent SMILE or FS-LASIK with refractive correction of −6.00 DS/−1.00 DC. Eight additional rabbits served as controls. Pre- and 24 hours, 1 week, 1 month, and 3 months postoperatively, slit-lamp and anterior segment optical coherence tomography were performed, followed by cornea and aqueous humor collection. Apoptosis and proliferation were evaluated with TUNEL assay and Ki-67 immunostaining, respectively. The mRNA and protein expression of cytokines and growth factors was determined by RT-qPCR and Western blotting, respectively. Cytokine levels in the aqueous humor were detected with ELISA.

          Results

          Compared with FS-LASIK, SMILE induced less apoptosis and proliferation in the cornea within 1 week postoperatively. Levels of IL-1β, TNF-α, and EGFR in the cornea were significantly increased after FS-LASIK compared with SMILE within 24 hours. Levels of IL-8 in the aqueous humor remained elevated until 1 week after FS-LASIK but not SMILE. TGF-β1 level was elevated up to 1 month after both procedures, while BFGF level was kept high within 1 month after SMILE but not FS-LASIK.

          Conclusions

          SMILE could induce significantly less acute inflammation than FS-LASIK in the cornea and aqueous humor. The differential expression of TGF-β1 and BFGF between two procedures until 1 month might contribute to the post-SMILE delayed recovery and underline the importance of continued treatment postoperatively.

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          Most cited references42

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          Progress in corneal wound healing.

          Alexander V. Ljubimov, Mehrnoosh Saghizadeh (2015)
          Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β (TGF-β) system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and nanocarriers for corneal drug delivery are discussed. Attention is also paid to problems in wound healing understanding and treatment, such as lack of specific epithelial stem cell markers, reliable identification of stem cells, efficient prevention of haze and stromal scar formation, lack of data on wound regulating microRNAs in keratocytes and endothelial cells, as well as virtual lack of targeted systems for drug and gene delivery to select corneal cells.
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            Refractive surgery

            Tae-im Kim, Jorge L Alió del Barrio, Mark A. Wilkins … (2019)
            Article 0 comments Cited 98 times – based on 0 reviews     Review now
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              Corneal biomechanical effects: small-incision lenticule extraction versus femtosecond laser-assisted laser in situ keratomileusis.

              S Wei, Yan-Wei Wang, Xin Tang … (2014)
              To compare the biomechanical properties of the cornea after small-incision lenticule extraction (lenticule extraction group) with those after femtosecond laser-assisted laser in situ keratomileusis (femtosecond LASIK group). Tianjin Eye Hospital & Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Medical University, Tianjin, China. Prospective comparative case series. Corneal hysteresis (CH), the corneal resistance factor (CRF), and 37 other biomechanical waveform parameters were quantitatively assessed with the Ocular Response Analyzer preoperatively and 1 week and 1, 3, and 6 months postoperatively. Each group comprised 40 eyes. The decrease in CH and the CRF was statistically significant 1 week postoperatively compared with preoperatively in both groups (P<.0001). However, the CH and CRF values in the lenticule extraction group were significantly higher than those in the femtosecond LASIK group 3 months and 6 months postoperatively (P<.032). The residual stromal thickness index versus the CRF and CH and the planned lenticule thickness versus the change in central corneal thickness were statistically significant in the lenticule extraction group (r = 0.388 to 0.950, P<.018); no significant correlation was found in the femtosecond LASIK group. In the waveform analysis of the lenticule extraction group, 28 of the 37 biomechanical waveform parameters differed significantly between preoperative values and postoperative values (P<.035). Both small-incision lenticule extraction and femtosecond laser-assisted LASIK can cause biomechanical changes in the cornea. However, changes in the cornea's viscoelastic properties were less after lenticule extraction than after LASIK. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2014. Published by Elsevier Inc.
              Article 0 comments Cited 55 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Invest Ophthalmol Vis Sci
                Journal ID (iso-abbrev): Invest. Ophthalmol. Vis. Sci
                Journal ID (pmc): iovs
                Journal ID (publisher-id): IOVS
                Title: Investigative Ophthalmology & Visual Science
                Publisher: The Association for Research in Vision and Ophthalmology
                ISSN (Print): 0146-0404
                ISSN (Electronic): 1552-5783
                Publication date (Electronic): 27 May 2020
                Publication date Collection: May 2020
                Volume: 61
                Issue: 5
                Electronic Location Identifier: 55
                Affiliations
                [ 1 ]School of Medicine, Nankai University, Tianjin, China
                [ 2 ]Department of Ophthalmology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
                [ 3 ]Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China
                [ 4 ]Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin, China
                [ 5 ]Department of Ophthalmology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China
                [ 6 ]Hong Kong Laser Center, Hong Kong SAR, China
                [ 7 ]Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
                [ 8 ]State Key Laboratory of Brain and Cognitive Sciences, University of Hong Kong, Hong Kong SAR, China
                Author notes
                [* ]Correspondence: Yan Wang, Tianjin Eye Hospital & Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Clinical College of Ophthalmology, Tianjin Medical University, Nankai University Eye Hospital, No 4. Gansu Road, He-ping District, Tianjin, 300020, China; wangyan7143@ 123456vip.sina.com ; ophwangyan@ 123456tmu.edu.cn.
                Kin Chiu, Department of Ophthalmology, State Key Laboratory of Brain and Cognitive Sciences, LKS Faculty of Medicine, University of Hong Kong, Rm. 410, Hong Kong Jockey Club Building for Interdisciplinary Research, 5 Sassoon Road, Pokfulam, Hong Kong SAR, China; datwai@ 123456hku.hk

                LL and WC contributed equally to this work and should be considered co-first authors.

                Article
                Publisher ID: IOVS-20-29510
                DOI: 10.1167/iovs.61.5.55
                PMC ID: 7405797
                PubMed ID: 32460319
                SO-VID: d31c233d-4efc-42bd-a5a0-fd032aec816c
                Copyright © Copyright 2020 The Authors
                License:

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                Date accepted : 13 April 2020
                Date received : 06 February 2020
                Page count
                Pages: 11
                Categories
                Subject: Cornea
                Subject: Cornea

                Keywords: smile,fs-lasik,cytokine,growth factors,delayed recovery
                Data availability:
                Keywords: smile, fs-lasik, cytokine, growth factors, delayed recovery

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