DOCSLIB.ORG

Sensory Nerve Supports Epithelial Stem Cell Function in Healing of Corneal Epithelium in Mice: the Role of Trigeminal Nerve Transient Receptor Potential Vanilloid 4

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Sensory Nerve Supports Epithelial Stem Cell Function in Healing of Corneal Epithelium in Mice: the Role of Trigeminal Nerve Transient Receptor Potential Vanilloid 4 Laboratory Investigation (2019) 99:210–230 https://doi.org/10.1038/s41374-018-0118-4 ARTICLE Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4 1 1 1 2 2 3 Yuka Okada ● Takayoshi Sumioka ● Kana Ichikawa ● Hiromi Sano ● Atsushi Nambu ● Kenta Kobayashi ● 4,5 4,5 4,5 6 7 8 Kunitoshi Uchida ● Yoshiro Suzuki ● Makoto Tominaga ● Peter Sol Reinach ● Syu-ichi Hirai ● James V. Jester ● 1 1 1 9 10 1 Masayasu Miyajima ● Kumi Shirai ● Hiroki Iwanishi ● Winston Whei-Yang Kao ● Chia-Yang Liu ● Shizuya Saika Received: 13 June 2018 / Revised: 6 July 2018 / Accepted: 9 July 2018 / Published online: 9 November 2018 © United States & Canadian Academy of Pathology 2018 Abstract In order to understand the pathobiology of neurotrophic keratopathy, we established a mouse model by coagulating the first branch of the trigeminal nerve (V1 nerve). In our model, the sensory nerve in the central cornea disappeared and remaining fibers were sparse in the peripheral limbal region. Impaired corneal epithelial healing in the mouse model was associated with suppression of both cell proliferation and expression of stem cell markers in peripheral/limbal epithelium as well as a 1234567890();,: 1234567890();,: reduction of transient receptor potential vanilloid 4 (TRPV4) expression in tissue. TRPV4 gene knockout also suppressed epithelial repair in mouse cornea, although it did not seem to directly modulate migration of epithelium. In a co-culture experiment, TRPV4-introduced KO trigeminal ganglion upregulated nerve growth factor (NGF) in cultured corneal epithelial cells, but ganglion with a control vector did not. TRPV4 gene introduction into a damaged V1 nerve rescues the impairment of epithelial healing in association with partial recovery of the stem/progenitor cell markers and upregulation of cell proliferation and of NGF expression in the peripheral/limbal epithelium. Gene transfer of TRPV4 did not accelerate the regeneration of nerve fibers. Sensory nerve TRPV4 is critical to maintain stemness of peripheral/limbal basal cells, and is one of the major mechanisms of homeostasis maintenance of corneal epithelium. Introduction such as mechanical or chemical injury or infection by microorganisms. Rapid healing of an epithelial defect in the Integrity of corneal epithelium is essential to maintain cornea is critical for the avoidance of infection and further proper vision by serving as a barrier against external stimuli damage to the underlying tissue. Cell migration and pro- liferation are both the main components of the process of corneal epithelial wound healing [1–3]. Healthy stem cells that locate to the basal layer of the limbal zone (around the Electronic supplementary material The online version of this article (https://doi.org/10.1038/s41374-018-0118-4) contains supplementary periphery of the cornea) play an important role in providing material, which is available to authorized users. daughter cells to the corneal epithelium for its repair [4, 5]. * Shizuya Saika Graduate University for Advanced Studies), Okazaki, Japan [email protected] 6 Wenzhou Medical University School of Ophthalmology and Optometry, Wenzhou, China 1 Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan 7 Educational Phyilosophy/Cell Biology, Wakayama Medical University School of Medicine, Wakayama, Japan 2 Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki, Japan 8 Department of Ophthalmology, School of Medicine, University of California, Irvine, Irvine, CA, USA 3 Section of Viral Vector Development, National Institute for Physiological Sciences, Okazaki, Japan 9 Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, OH, USA 4 Division of Cell Signaling, National Institute for Physiological Sciences, Okazaki, Japan 10 School of Optometry, Indiana University Bloomington, Bloomington, IN, USA 5 Department of Physiological Sciences, SOKENDAI (The Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role. 211 Various growth factors are believed to orchestrate the epi- One of the presumed reasons why there is currently no thelial cell behaviors during tissue repair [1–3]. Among effective therapy for neurotrophic keratopathy might be the them, nerve growth factor (NGF) and its receptors, p75 and fact that a suitable experimental mouse model is not avail- TrkA, are reportedly involved in maintenance of stemness able. Ferrari et al. [37] developed a trigeminal stereotactic of limbal basal cells with high proliferating potential [6–9]. electrolysis model of clinical neurotrophic keratitis and The cornea is one of the most densely innervated tissues found that corneal denervation by this procedure resulted in with ophthalmic sensory terminal branches of the trigeminal breakdown of the integrity of corneal epithelium and was nerve [10–13]. Nerve fibers enter the limbus and the per- associated with increased apoptosis and reduced prolifera- ipheral cornea and distribute over the cornea in a radial tion of epithelial cells. We obtained a similar result by pattern. Then, the fibers penetrate the Bowman’s membrane employing a procedure with stereotactic intracranial coa- upward and distribute beneath epithelial basal cells, forming gulation of the first branch of the trigeminal nerve by using the sub-basal nerve plexus that supplies the overlying cor- an 18-guage needle (supplemental data 1). We herein show neal epithelium [10, 14]. Interaction between sensory nerve that use of a 20-guage needle in the same stereotactic pro- and local tissues, i.e., skin or epithelia of internal organs, is cedure reduced the damage of the first branch of the tri- required for the homeostasis of the tissue [15–20]. Healthy geminal nerve and produced a mouse model of neurotrophic innervation is essential to the maintenance of corneal keratopathy more similar to clinical cases. This mouse structure and function, i.e., barrier function, proliferation, model of neurotrophic keratopathy exhibits a normal- differentiation or wound healing. In turn, impaired sensory looking cornea without obvious tissue inflammation under innervation or function may impair homeostasis of the physiological conditions, but impairment of epithelial corneal epithelium, leading to persistent disorders or wound healing is apparent upon epithelial debridement. Our abnormal repair in the tissue (neurotrophic keratopathy) detailed analysis showed delayed epithelial healing was [21–23]. It was reported that sensory innervation plays an attributable to the loss of stemness and cell proliferation important role in maintenance of stemness of limbal basal caused by sensory denervation in peripheral/limbal epithe- epithelial cells by expressing ATP-binding cassette sub- lium. In the current investigation, we employed this mouse family G member 2 (ABCG2), p63 and hairy enhancer of model of neurotrophic keratopathy. split 1 (Hes1), a Notch signal-related component [24]. The Transient receptor potential (TRP) channels constitute a causes of impaired trigeminal sensation include direct injury superfamily of 28 genes that are subdivided into 7 sub- to the intracranial trigeminal nerve by brain trauma or families, including TRP vanilloid (TRPV) and TRP ankyrin tumor, diabetes mellitus, herpes virus infection or injury in type (TRPA), among others. Each TRP superfamily mem- the sensory nerve fibers in the corneal tissue by trauma or bers is a nonselective cation channel that possesses variable surgery such as corneal refractive surgery [25–29]. Ca2+ permeability and acts as a sensor to a wide array of Although the causes of neurotrophic keratopathy are evi- inputs, including temperature, pressure, pH alteration, che- dent in many cases, neurotrophic keratopathy is refractory micals and lipids. In skin, many of the TRP family members to classical treatments, which include wearing a bandage are expressed in both keratinocytes and in sensory nerve contact lens, tarsorrhaphy or supplementation with an arti- fibers and are involved in sensing and maintaining tissue ficial tear solution [30–32]. Refractory persistent corneal homeostasis [38]. In the cornea, TRP channel subtypes from epithelial neurotrophic keratopathy could lead to corneal different subfamilies are involved in mediating responses to stromal perforation, with or without intraocular infection, injuries that affect the process of wound healing. We pre- that could potentially cause widespread destruction of eye viously reported that the loss of either TRPV1, TRPV4 or tissue and permanent severe vision loss. Sosne et al. [33] TRPA1 attenuates excessive inflammatory fibrogenic reac- reported the potential efficacy of thymosin β4 in the treat- tion in a mouse cornea injured by an alkali exposure, and is ment of this condition. The notion that neuropeptides could minimally dependent on the genotype of inflammatory cells have a promoting effect on epithelial healing in the cornea [39–41]. On the other hand, we also previously showed that was first proposed by Nishida and Yanai [34]. They blockage of TRPV1 activation or TRPV1 gene ablation reported that topical application of a combination of pep- suppressed healing of defective epithelial animal corneas in tides derived from insulin-like growth factor and substance association with suppression of expression of substance P P exerts a significant therapeutic effect on refractory corneal and interleukin-6
Load more

Recommended publications
  • Cultivating a Cure for Blindness
    news and views were taken in a l-mm2 biopsy from the good eye, then they were cultured and, on second Cultivating a cure passage, they formed a tightly packed and communicating (confluent) monolayer of cells. For grafting, the conjunctiva! epi­ for blindness thelium was completely removed from the cornea and limbus of the recipient eye, and replaced with a slightly larger monolayer of Stuart Hodson cultured limbal epithelium. The eyes were Damaged corneas can often be repaired using donor grafts, but if the then covered with therapeutic soft contact damage is too great the graft wlll be rejected. This may change with the lenses, and tightly patched for several days. development of a method to Inhibit rejection which uses cultivated cells. The results after the limbal epithelial graft were very promising. The grafted epithelium he human cornea has a special proper­ epithelium can mould a smooth apical and was stable, transparent, multi-layered and Tty known as immune privilege, which basal surface, the limbal epithelial stem cells smooth. One of the patients had suffered an allows tissue grafts from donors to be do not form such a smooth surface. alkali burn to his left eye ten years earlier, and carried out without the usual problems of If the corneal epithelium is lost it can be had undergone three previous unsuccessful immune rejection. However, immune privi­ functionally regenerated by the limbal stem corneal grafts. Before the treatment he had lege is lost at the perimeter of the cornea - cells. But if both the corneal and limbal continual severe corneal vascularization the limb us of the eye - where the transpar­ epithelia are lost, the corneal surface is re­ ( development of blood vessels) and persis­ ent corneal stroma meets the opaque sclera colonized by the other neighbour of the tent ulceration, and the eye was painful and (Fig.
    [Show full text]
  • Quantitative Assessment of Central and Limbal Epithelium After Long
    Eye (2016) 30, 979–986 © 2016 Macmillan Publishers Limited All rights reserved 0950-222X/16 www.nature.com/eye 1,5 1,5 1 Quantitative RK Prakasam , BS Kowtharapu , K Falke , CLINICAL STUDY K Winter2,3, D Diedrich4, A Glass4, A Jünemann1, assessment of central RF Guthoff1 and O Stachs1 and limbal epithelium after long-term wear of soft contact lenses and in patients with dry eyes: a pilot study Abstract Purpose Analysis of microstructural Eye (2016) 30, 979–986; doi:10.1038/eye.2016.58; alterations of corneal and limbal epithelial published online 22 April 2016 cells in healthy human corneas and in other ocular conditions. Introduction Patients and methods Unilateral eyes of three groups of subjects include healthy The X, Y, Z hypothesis1 explains cell mechanism volunteers (G1, n = 5), contact lens wearers that is essential for the renewal and maintenance 1Department of (G2, n = 5), and patients with dry eyes of the corneal epithelium. This hypothesis Ophthalmology, University = proposes that the loss of corneal epithelial of Rostock, Rostock, (G3, n 5) were studied. Imaging of basal Germany (BC) and intermediate (IC) epithelial cells surface cells (Z) can be maintained by the from central cornea (CC), corneal limbus proliferation of basal epithelial cells (X), and the 2Faculty of Medicine, centripetal movements of the peripheral (CL) and scleral limbus (SL) was obtained by Institute of Anatomy, epithelial cells (Y). By utilizing this mechanism, University of Leipzig, in vivo confocal microscopy (IVCM). An it is also possible to categorize both disease and Leipzig, Germany appropriate image analysis algorithm was therapies according to the specific component 3 used to quantify morphometric parameters involved.1 Therefore it is vital to understand the Institute for Medical including mean cell area, compactness, Informatics, Statistics and cellular structures of both central and limbal Epidemiology (IMISE), solidity, major and minor diameter, and epithelial cells in normal and in various corneal University of Leipzig, maximum boundary distance.
    [Show full text]
  • Development of in Vitro Corneal Models: Opportunity for Pharmacological Testing
    Review Development of In Vitro Corneal Models: Opportunity for Pharmacological Testing Valentina Citi 1, Eugenia Piragine 1, Simone Brogi 1,* , Sara Ottino 2 and Vincenzo Calderone 1 1 Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy; [email protected] (V.C.); [email protected] (E.P.); [email protected] (V.C.) 2 Farmigea S.p.A., Via G.B. Oliva 6/8, 56121 Pisa, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-050-2219-613 Received: 24 October 2020; Accepted: 30 October 2020; Published: 2 November 2020 Abstract: The human eye is a specialized organ with a complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years, many in vitro models have been developed in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review, the ocular cell types and functionality are described, providing an overview about the scientific challenge for the development of three-dimensional (3D) in vitro models.
    [Show full text]
  • Vocabulario De Morfoloxía, Anatomía E Citoloxía Veterinaria
    Vocabulario de Morfoloxía, anatomía e citoloxía veterinaria (galego-español-inglés) Servizo de Normalización Lingüística Universidade de Santiago de Compostela COLECCIÓN VOCABULARIOS TEMÁTICOS N.º 4 SERVIZO DE NORMALIZACIÓN LINGÜÍSTICA Vocabulario de Morfoloxía, anatomía e citoloxía veterinaria (galego-español-inglés) 2008 UNIVERSIDADE DE SANTIAGO DE COMPOSTELA VOCABULARIO de morfoloxía, anatomía e citoloxía veterinaria : (galego-español- inglés) / coordinador Xusto A. Rodríguez Río, Servizo de Normalización Lingüística ; autores Matilde Lombardero Fernández ... [et al.]. – Santiago de Compostela : Universidade de Santiago de Compostela, Servizo de Publicacións e Intercambio Científico, 2008. – 369 p. ; 21 cm. – (Vocabularios temáticos ; 4). - D.L. C 2458-2008. – ISBN 978-84-9887-018-3 1.Medicina �������������������������������������������������������������������������veterinaria-Diccionarios�������������������������������������������������. 2.Galego (Lingua)-Glosarios, vocabularios, etc. políglotas. I.Lombardero Fernández, Matilde. II.Rodríguez Rio, Xusto A. coord. III. Universidade de Santiago de Compostela. Servizo de Normalización Lingüística, coord. IV.Universidade de Santiago de Compostela. Servizo de Publicacións e Intercambio Científico, ed. V.Serie. 591.4(038)=699=60=20 Coordinador Xusto A. Rodríguez Río (Área de Terminoloxía. Servizo de Normalización Lingüística. Universidade de Santiago de Compostela) Autoras/res Matilde Lombardero Fernández (doutora en Veterinaria e profesora do Departamento de Anatomía e Produción Animal.
    [Show full text]
  • A Technique for Obtaining Basal Corneal Epithelial Cells
    Reports A Technique for Obtaining Basal Corneal Epithelial Cells V. Trinkaus-Randall and I. K. Gipson A technique has been developed for obtaining a cell suspen- basal cells can be freed from the basal laminae after sion enriched (89%) in basal corneal epithelial cells. Eleven an incubation with Dispase II.8 millimeter corneal buttons were removed and placed in Materials and Methods. All investigations involving culture medium containing low (10 nM) calcium. The animals reported in this study conform to the ARVO posterior half of the stroma was removed with forceps. Resolution on the Use of Animals in Research. New Three superficial cuts were made with a Bard-Parker blade on the anterior half of the cornea, which was then incubated Zealand white rabbits were killed by administering 5 for 18 hr at 35°C. Nonadherent cells were brushed off after ml pentobarbital (325 mg) intravenously. An outline the incubation and basal cells were harvested after a 1-hr was made on the cornea with an 11-mm trephine incubation in Dispase II. Cell viability estimated by Eryth- and corneal buttons were cut free with scissors. The rocin /? exclusion was 90%. Further evidence of viability posterior half of the stroma then was pulled away was that the cells adhered to their native substrate, the from the cornea with jewelers' forceps. Three evenly denuded basal lamina. The authors protocol provides a spaced, superficial cuts (1 mm in length) were made method for analyzing the biochemistry of a known population on the cornea with a small scalpel to facilitate the of epithelial cells and makes available a defined source of penetration of the medium.
    [Show full text]
  • Maintaining the Cornea and the General Physiological Environment in Visual Neurophysiology Experiments
    Journal of Neuroscience Methods 109 (2001) 153–166 www.elsevier.com/locate/jneumeth Maintaining the cornea and the general physiological environment in visual neurophysiology experiments Andrew B. Metha a, Alison M. Crane b , H. Grady Rylander III c, Sharon L. Thomsen d, Duane G. Albrecht b,* a Department of Optometry and Vision Sciences, The Uni6ersity of Melbourne, Carlton, Victoria 3053, Australia b Department of Psychology, Uni6ersity of Texas, Austin, TX 78712, USA c Department of Electrical and Computer Engineering, Uni6ersity of Texas, Austin, TX 78712, USA d Biomedical Engineering Program, Uni6ersity of Texas, Austin, TX 78712, USA Received 30 January 2001; received in revised form 4 June 2001; accepted 4 June 2001 Abstract Neurophysiologists have been investigating the responses of neurons in the visual system for the past half-century using monkeys and cats that are anesthetized and paralyzed, with the non-blinking eyelids open for prolonged periods of time. Impermeable plastic contact lenses have been used to prevent dehydration of the corneal epithelium, which would otherwise occur in minutes. Unfortunately, such lenses rapidly introduce a variety of abnormal states that lead to clouding of the cornea, degradation of the retinal image, and premature termination of the experiment. To extend the viability of such preparations, a new protocol for maintenance of corneal health has been developed. The protocol uses rigid gas permeable contact lenses designed to maximize gas transmission, rigorous sterile methods, and a variety of methods for sustaining and monitoring the overall physiology of the animal. The effectiveness of the protocol was evaluated clinically by ophthalmoscopy before, during, and after the experiments, which lasted 8–10 days.
    [Show full text]
  • Changes in Epithelial and Stromal Corneal Stiffness Occur with Age
    bioengineering Article Changes in Epithelial and Stromal Corneal Stiffness Occur with Age and Obesity Peiluo Xu 1, Anne Londregan 2 , Celeste Rich 3 and Vickery Trinkaus-Randall 3,4,* 1 Department of Biomedical Engineering, Boston University, Boston, MA 02115, USA; [email protected] 2 Department of Biochemistry/Molecular Biology, Boston University, Boston, MA 02215, USA; [email protected] 3 Department of Biochemistry, Boston University School of Medicine, Boston, MA 02115, USA; [email protected] 4 Department of Ophthalmology, Boston University School of Medicine, Boston, MA 02115, USA * Correspondence: [email protected] Received: 14 January 2020; Accepted: 4 February 2020; Published: 7 February 2020 Abstract: The cornea is avascular, which makes it an excellent model to study matrix protein expression and tissue stiffness. The corneal epithelium adheres to the basement zone and the underlying stroma is composed of keratocytes and an extensive matrix of collagen and proteoglycans. Our goal was to examine changes in corneas of 8- and 15-week mice and compare them to 15-week pre-Type 2 diabetic obese mouse. Nanoindentation was performed on corneal epithelium in situ and then the epithelium was abraded, and the procedure repeated on the basement membrane and stroma. Confocal imaging was performed to examine the localization of proteins. Stiffness was found to be age and obesity dependent. Young’s modulus was greater in the epithelium from 15-week mice compared to 8-week mice. At 15 weeks, the epithelium of the control was significantly greater than that of the obese mice. There was a difference in the localization of Crb3 and PKCζ in the apical epithelium and a lack of lamellipodial extensions in the obese mouse.
    [Show full text]
  • Application of Collagen I and IV in Bioengineering Transparent Ocular Tissues
    REVIEW published: 26 August 2021 doi: 10.3389/fsurg.2021.639500 Application of Collagen I and IV in Bioengineering Transparent Ocular Tissues Yihui Song 1†, Morgan Overmass 1†, Jiawen Fan 2, Chris Hodge 1,3,4, Gerard Sutton 1,3,4, Frank J. Lovicu 1,5 and Jingjing You 1,6* 1 Save Sight Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia, 2 Key Laboratory of Myopia of State Health Ministry, Department of Ophthalmology and Vision Sciences, Eye and Ear, Nose, and Throat (ENT) Hospital, Shanghai Medical College, Fudan University, Shanghai, China, 3 New South Wales (NSW) Tissue Bank, Sydney, NSW, Australia, 4 Vision Eye Institute, Chatswood, NSW, Australia, 5 Discipline of Anatomy and Histology, School of Medical Sciences, The University of Sydney, Sydney, NSW, Australia, 6 School of Optometry and Vision Science, University of New South Wales, Sydney, NSW, Australia Collagens represent a major group of structural proteins expressed in different tissues and display distinct and variable properties. Whilst collagens are non-transparent in the skin, they confer transparency in the cornea and crystalline lens of the eye. There are 28 types of collagen that all share a common triple helix structure yet differ in the composition Edited by: of their α-chains leading to their different properties. The different organization of collagen Zhilian Yue, fibers also contributes to the variable tissue morphology. The important ability of collagen University of Wollongong, Australia to form different tissues has led to the exploration and application of collagen as a Reviewed by: biomaterial. Collagen type I (Col-I) and collagen type IV (Col-IV) are the two primary Tiago H.
    [Show full text]
  • Corneal Erosion?
    What Is the Cornea? The cornea is the clear front window of the eye. It covers the iris (colored portion of the eye) and the round pupil, much like a watch crystal covers the face of a watch. The cornea is composed of five layers. The outermost surface layer is called the epithelium. Normal Eye Anatomy What Is a Corneal Abrasion? A corneal abrasion is an injury (a scratch, scrape or cut) to the corneal epithelium. Abrasions are commonly caused by fingernail scratches, paper cuts, makeup brushes, scrapes from tree or bush limbs, and rubbing of the eye. Some eye conditions, such as dry eye, increase the chance of an abrasion. You may experience the following symptoms with corneal abrasion: • Feeling of having something in your eye • Pain and soreness of the eye • Redness of the eye • Sensitivity to light • Tearing • Blurred vision To detect an abrasion on the cornea, your ophthalmologist (Eye M.D.) will use a special dye called fluorescein (pronounced FLOR-uh-seen) to illuminate the injury. How Is a Corneal Abrasion Treated? Treatment may include the following: • Patching the injured eye to prevent eyelid blinking from irritating the injury. • Applying lubricating eyedrops or ointment to the eye to form a soothing layer between the eyelid and the abrasion. • Using antibiotics to prevent infection. • Dilating (widening) the pupil to relieve pain. • Wearing a special contact lens to help healing. Minor abrasions usually heal within a day or two; larger abrasions usually take about a week. It is important not to rub the eye while it is healing.
    [Show full text]
  • Anatomy & Physiology of The
    Anatomy & Physiology of The Eye 2017-2018 Done By: 433 Team Abdullah M. Khattab Important Doctor’s Notes Extra Abdullah AlOmair Resources: Team 433, Doctors Notes, Vaughan & Asbury’s General ophthalmology. Editing File Embryology of The Eye ............................................................................................. 2 ● Defects: ........................................................................................................................... 2 Development of The Eye After Birth .......................................................................... 3 ● Refractive power depends on two factors: ...................................................................... 3 The Orbit ................................................................................................................... 4 ● Seven bones contribute the bony orbit and surrounded by nasal sinuses. .................... 4 ● The orbital wall, pear-like shaped, formed by: ................................................................ 4 ● Structures Passing Through the Optic Openings: ........................................................... 4 Extraocular Muscles .................................................................................................. 1 ● Anatomy .......................................................................................................................... 1 ● Notes: .............................................................................................................................. 1 ● Field of action:
    [Show full text]
  • Immunohistochemical Mapping of Corneal Sensory Innervation in Mice: Effects of Sjögren`S Syndrome Associated Dry Eye
    IMMUNOHISTOCHEMICAL MAPPING OF CORNEAL SENSORY INNERVATION IN MICE: EFFECTS OF SJÖGREN`S SYNDROME ASSOCIATED DRY EYE By RENATA VELLOSO RAMOS A THESIS PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE UNIVERSITY OF FLORIDA 2016 © 2016 Renata Velloso Ramos To Viviane and Otto ACKNOWLEDGMENTS I would like to recognize and express my profound gratitude to my advisor Dr. Caryn Plummer for believing in me and giving me the opportunity of pursing my Master of Science degree and residency under her mentorship. I am greatly thankful for her guidance, encouragement, and friendship. I admire her remarkable ability to mentor, lead and teach while also being a caring friend; she will always be a professional model for me. I would like to extend my sincere gratitude to my co-advisor Dr. Rick Johnson for helping me in the development of critical thinking and commitment to high quality research. I am very honored to be able to benefit from his guidance, experience and friendship. I would like to thank Dr. Whitley, Dr. Brooks and Dr. Hamor for their intellectual guidance, support and enthusiasm in both research and clinical settings. I would like to express my gratitude to Dr. Cuong Nguyen, for the use of his mouse colony also offering his knowledge and support. I extend my appreciation to Dr. Dan Gibson and Dr. Jasenka Zubcevic for their continued input, interest and brilliant solutions along the way. Their encouragement helped me to transform moments worth of frustration into a successful endeavor.
    [Show full text]
  • Corneal Epithelial Stem Cells: Past, Present, and Future
    Corneal Epithelial Stem Cells: Past, Present, and Future Tung-Tien Sun,Ã and Robert M. Lavkerw ÃEpithelial Biology Unit, Departments of Dermatology, Pharmacology and Urology, NYU Cancer Institute, New York University School of Medicine, New York, New York, USA; wDepartment of Dermatology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois, USA Corneal epithelium is a self-renewing tissue. Recent studies indicate that corneal epithelial stem cells reside pref- erentially in the basal layer of peripheral cornea in the limbal zone, rather than uniformly in the entire corneal epithelium. This idea is supported by a unique limbal/corneal expression pattern of the K3 keratin marker for corneal- type differentiation; the preferential distribution of the slow-cycling (label-retaining) cells in the limbus; the superior proliferative capacity of limbal cells as compared with central corneal epithelial cells in vitro and in vivo; and the ability of limbal basal cells to rescue/reconstitute severely damaged or completely depleted corneal epithelium upon transplantation. The limbal/stem cell concept provides explanations for several paradoxical properties of corneal epithelium including the predominance of tumor formation in the limbal zone, the centripetal migration of peripheral corneal cells toward the central cornea, and the ‘‘mature-looking’’ phenotype of the corneal basal cells. The limbal stem cell concept has led to a better understanding of the strategies that a stratified squamous epithelium uses in repair, to a new
    [Show full text]