An In-Silico Study on the Most Effective Growth Factors in Retinal Regeneration Utilizing Tissue Engineering Concepts

Purpose: Considering the significance of retinal disorders and the growing need to employ tissue engineering in this field, in-silico studies can be used to establish a cost-effective method. This in-silico study was performed to find the most effective growth factors contributing to retinal tissue engineering. Methods: In this study, a regeneration gene database was used. All 21 protein-coding genes participating in retinal regeneration were considered as a protein–protein interaction (PPI) network via the “STRING App” in “Cytoscape 3.7.2” software. The resultant graph possessed 21 nodes as well as 37 edges. Gene ontology (GO) analysis, as well as the centrality analysis, revealed the most effective proteins in retinal regeneration. Results: According to the biological processes and the role of each protein in different pathways, selecting the correct one is possible through the information that the network provides. Eye development, detection of the visible light, visual perception, photoreceptor cell differentiation, camera-type eye development, eye morphogenesis, and angiogenesis are the major biological processes in retinal regeneration. Based on the GO analysis, SHH, STAT3, FGFR1, OPN4, ITGAV, RAX, and RPE65 are effective in retinal regeneration via the biological processes. In addition, based on the centrality analysis, four proteins have the greatest influence on retinal regeneration: SHH, IGF1, STAT3, and ASCL1. Conclusion: With the intention of applying the most impressive growth factors in retinal engineering, it seems logical to pay attention to SHH, STAT3, and RPE65. Utilizing these proteins can lead to fabricate high efficiency engineered retina via all aforementioned biological processes

Long-term Outcome of Limbal Stem Cell Transplantation for Management of Total Limbal Stem Cell Deficiency due to Chemical Burn

 Purpose: To evaluate the long-term outcome of limbal stem cell transplantation for management of total limbal stem cell deficiency due to chemical burn. Patients and Methods: In this retrospective cross sectional study; records of patients with history of severe (grade III to IV) chemical burns who underwent limbal stem cell transplantation in Labbafinejad Medical Center, Tehran, Iran between 2006 and 2016 were reviewed and data including demographic characteristics, visual acuity, surgical interventions and outcomes were reported. Results: Fifty eyes of fifty patients with a history of conjunctival limbal autograft (N = 24) or keratolimbal allograft (N = 26) with at least 12-months follow-up were included. The overall 1-year and 5-year survival was 100 % and 84.1 % for conjunctival limbal autograft and 80.4 % and 40 % for keratolimbal allograft, respectively (P = 0.037). Corneal transplantation was performed after limbal stem cell transplantation in 20 eyes after conjunctival limbal autograft and 25 eyes after keratolimbal allograft. The 1-year and 5-year corneal graft survival was 93.3 % and 63.8 % after conjunctival limbal autograft and 92 % and 38.4 % after keratolimbal allograft (P = 0.005 for five year survival). There was a significant improvement in LogMAR BCVA (1.79 versus 2.17, P < 0.001) in all patients with no statistically significant difference between the two groups. Conclusion: Severe chemical burn is associated with significant ocular morbidity and long-term prognosis is poor. Graft survival rate was significantly better in conjunctival limbal autograft compared to keratolimbal allograft when comparing the Long-term outcome of limbal stem cell transplantation for management of total limbal stem cell deficiency due to chemical burn.Keywords: Limbus Cornea, Stem Cell, Transplantation, Cornea, Eye Burns   

The Ocular Surface Chemical Burns

Ocular chemical burns are common and serious ocular emergencies that require immediate and intensive evaluation and care. The victims of such incidents are usually young, and therefore loss of vision and disfigurement could dramatically affect their lives. The clinical course can be divided into immediate, acute, early, and late reparative phases. The degree of limbal, corneal, and conjunctival involvement at the time of injury is critically associated with prognosis. The treatment starts with simple but vision saving steps and is continued with complicated surgical procedures later in the course of the disease. The goal of treatment is to restore the normal ocular surface anatomy and function. Limbal stem cell transplantation, amniotic membrane transplantation, and ultimately keratoprosthesis may be indicated depending on the patients’ needs

Indications for Corneal Transplantation at a Tertiary Referral Center in Tehran

Purpose: To report the indications and techniques of corneal transplantation at a tertiary referral center in Tehran over a 3-year period. Methods: Records of patients who had undergone any kind of corneal transplantation at Labbafinejad Medical Center, Tehran, Iran from March 2004 to March 2007 were reviewed to determine the indications and types of corneal transplantation. Results: During this period, 776 eyes of 756 patients (including 504 male subjects) with mean age of 41.3±21.3 years underwent corneal transplantation. The most common indication was keratoconus (n=317, 40.8%) followed by bullous keratopathy (n=90, 11.6%), non-herpetic corneal scars (n=62, 8.0%), infectious corneal ulcers (n=61, 7.9%), previously failed grafts (n=61, 7.9%), endothelial and stromal corneal dystrophies (n=28, 3.6%), and trachoma keratopathy (n=26, 3.3%). Other indications including Terrien′s marginal degeneration, post-LASIK keratectasia, trauma, chemical burns, and peripheral ulcerative keratitis constituted the rest of cases. Techniques of corneal transplantation included penetrating keratoplasty (n=607, 78.2%), deep anterior lamellar keratoplasty (n=108, 13.9%), conventional lamellar keratoplasty (n=44, 5.7%), automated lamellar therapeutic keratoplasty (n=8, 1.0%), and Descemet stripping endothelial keratoplasty (n=6, 0.8%) in descending order. The remaining cases were endothelial keratoplasty and sclerokeratoplasty. Conclusion: In this study, keratoconus was the most common indication for penetrating keratoplasty which was the most prevalent technique of corneal transplantation. However, deep anterior lamellar keratoplasty is emerging as a growing alternative for corneal pathologies not involving the endothelium

Design and characterization of biodegradable multi layered electrospun nanofibers for corneal tissue engineering applications

YesTissue engineering is one of the most promising areas for treatment of various ophthalmic diseases particularly for patients who suffer from limbal stem cell deficiency and this is due to the lack of existence of appropriate matrix for stem cell regeneration. The aim of this research project is to design and fabricate triple layered electrospun nanofibers as a suitable corneal tissue engineering scaffold and the objective is to investigate and perform various in vitro tests to find the most optimum and suitable scaffold for this purpose. Electrospun scaffolds were prepared in three layers. Poly(d, l-lactide-co-glycolide; PLGA, 50:50) nanofibers were electrospun as outer and inner layers of the scaffold and aligned type I collagen nanofibers were electrospun in the middle layer. Furthermore, the scaffolds were cross-linked by 1-ethyl-3-(3 dimethylaminopropyl) carbodiimide hydrochloride and glutaraldehyde. Structural, physical, and mechanical properties of scaffolds were investigated by using N2 adsorption/desorption isotherms, Fourier transform infrared spectroscopy, contact angle measurement, tensile test, degradation, shrinkage analysis, and scanning electron microscopy (SEM). In addition, capability to support cell attachment and viability were characterized by SEM, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and 4′,6-diamidino-2-phenylindole staining. According to the result of Brunauer–Emmett–Teller analysis, specific surface area of electrospun scaffold was about 23.7 m2 g-1. Tensile tests on cross-linked scaffolds represented more suitable hydrophilicity and tensile behavior. In addition, degradation rate analysis indicated that noncross-linked scaffolds degraded faster than cross-linked one and cross-linking led to controlled shrinkage in the scaffold. The SEM analysis depicted nano-sized fibers in good shape. Also, the in vitro study represented an improved cell attachment and proliferation in the presence of human endometrial stem cells for both cross-linked and noncross-linked samples. The current study suggests the possibility of producing an appropriate substrate for successful cornea tissue engineering with a novel design.Deputy of Research, Tehran University of Medical Science. Grant Number: 93‐01‐33‐2561