DOCSLIB.ORG

KLEIP Deficiency in Mice Causes Progressive Corneal Neovascular

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
KLEIP Deficiency in Mice Causes Progressive Corneal Neovascular Cornea KLEIP Deficiency in Mice Causes Progressive Corneal Neovascular Dystrophy Nicole Hahn,1,2 Christian T. Dietz,1 Sandra Kuhl,¨ 1 Urs Vossmerbaeumer,3 and Jens Kroll1,2 PURPOSE. The BTB-kelch protein KLEIP/KLHL20 is an actin linked to corneal dystrophy formation. For example, genomic binding protein that regulates cell-cell contact formation and mutations in the keratin-3 and keratin-12 genes are linked to an cell migration. The aim of our study was to characterize epithelial dystrophy phenotype, called Meesmann dystrophy,4 KLEIP’s function in ocular health and disease in mice. and gene mutations in the transforming growth factor-b- induced (TGFBI) gene can cause corneal dystrophies, such as METHODS. KLEIP-/- mice were generated, and corneas were Reis-Bucklers¨ dystrophy, Thiel-Behnke dystrophy, and granular examined histologically and stained for keratin-1, loricrin, type 1-, granular type 2-, and lattice type 1-dystrophy in keratin-12, keratin-14, CD31, LYVE-1, F4/80, E-cadherin, and humans.5 Ki67. Corneal abrasions were performed after eyelid opening. Genetic animal models to study onset, progression, and RESULTS. Corneas of KLEIPþ/þ and KLEIP-/- mice were therapeutic intervention of corneal dystrophies currently are indistinguishable at birth. After eyelid opening corneal very limited. For example, keratin-12, a protein that forms epithelial hyperplasia started to manifest in KLEIP-/- mice, intermediate filaments in epithelial cells, is expressed specif- showing a progressive epithelial metaplasia leading to total ically in the corneal epithelium in mice.6 Its gene silencing corneal opacity. In KLEIP-/- mice the initial stratified resulted in a fragile epithelium serving as a mouse model for squamous corneal epithelium was altered to an epidermal Meesmann corneal dystrophy.7 In addition to the keratins, histo-architecture showing several superficial keratinized cells, genetic alterations in different proteoglycans can induce cell infiltrations into the stroma, and several apoptotic cells. corneal malformations in mice. For example deletion of Skin markers keratin 1 and loricrin were positive, and surface keratocan, a cornea-specific keratan sulphate proteoglycan, disease was accompanied by deep stromal vascularization. resulted in a thinner corneal stroma8 and lumican, which gene Expression analysis for E-cadherin in KLEIP-/- corneas showed inactivation in mice showed a cloudy and thin corneal stroma.9 acellular areas in the squamous epithelium, indicating a Another class of molecules that can cause corneal dystrophies progressive fragile corneal integrity. Removal of the virgin in mice are transcription factors. Corneal-specific overexpres- epithelium accelerated strongly development of the epithelial sion of the transcription factor Pax6 induced an abnormal and stromal alterations, identifying mechanical injuries as the cornea with altered epithelial cell morphology and neovascu- major trigger for corneal dystrophy formation and scarification larization;10 inactivation of zinc finger transcription factor in KLEIP-/- mice. Zeb1 in mice correlated with the posterior polymorphous corneal dystrophy,11 and tissue-specific deletion of transcrip- CONCLUSIONS. The data identify KLEIP as an important molecule tion factor Pbx1 in the corneal epithelium resulted in a corneal regulating corneal epithelial integrity. (Invest Ophthalmol Vis dystrophy and clouding.12 Moreover, genetic inactivation of Sci. 2012;53:3260–3268) DOI:10.1167/iovs.12-9676 the transcriptions factors AP-2alpha, Klf4, Klf5, and Cited2 also induced corneal defects in mice.13–16 Together, these mouse models identified few genes that can cause corneal alterations rogredient opacity of the cornea due to stromal reorgani- in mice, but it is unclear mostly whether these genes can cause Pzation, keratinization of the corneal epithelium and 17 1–3 corneal dystrophies in patients as well. Moreover, based on neovascularization, is a major reason for blindness in man. the diversity of corneal dystrophies in patients, several In humans, only few genes have been identified so far that are potential molecular regulators for corneal dystrophy formation still are not yet identified. The BTB-kelch protein KLEIP (Kelch-like ECT2 interacting From the 1Department of Vascular Biology and Tumor Angio- protein), also named KLHL20, has been identified first in genesis, Center for Biomedicine and Medical Technology Mannheim MDCK cells where it co-localizes transiently with F-actin during (CBTM), Medical Faculty Mannheim, Heidelberg University, Man- 18 2 the process of cell-cell contact induction. Recruitment of nheim, Germany; the Division of Vascular Oncology and Metastasis, KLEIP to cell adhesion sites depends on Rac1 activation and German Cancer Research Center (DKFZ-ZMBH Alliance), Heidel- 18 berg, Germany, and the 3Department of Ophthalmology, Mainz requires E-cadherin. In addition, KLEIP is induced under 19 University Medical Center, Mainz, Germany. hypoxic conditions that can stimulate RhoA signaling during 20,21 Supported by the Deutsche Forschungsgemeinschaft (KR1887/ endothelial cell migration and in neurite outgrowth. 4-3, KR1887/5-1, and INST 91027/10-1 FUGG). Recent findings also identified KLEIP as a molecule acting Submitted for publication February 10, 2012; revised March 28, together with the wnt/beta-catenin signaling pathway, which 2012; accepted April 9, 2012. may regulate skin thickness.22 In summary, the data highlight Disclosure: N. Hahn,None;C.T. Dietz,None;S. K¨uhl,None; KLEIP as an important molecule in cell-cell contact formation, U. Vossmerbaeumer,None;J. Kroll,None regulation of the cellular architecture, and cellular reorganiza- Corresponding author: Jens Kroll, Center for Biomedicine and tion, and identified KLEIP as a factor regulating cell migration. Medical Technology Mannheim (CBTM), Dept. of Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim, Heidelberg Yet, its function in vivo still is unknown. University, Germany, Ludolf-Krehl-Str. 13-17, 68167 Mannheim, To address KLEIP’s function in vivo, we have generated Germany; Telephone þ49-(0)621-383-9965; Fax þ49-(0)621-383- KLEIP knockout mice, and identified KLEIP as an essential 9961; [email protected]. component for the maintenance of corneal integrity. KLEIP-/- Investigative Ophthalmology & Visual Science, May 2012, Vol. 53, No. 6 3260 Copyright 2012 The Association for Research in Vision and Ophthalmology, Inc. Downloaded from iovs.arvojournals.org on 09/30/2021 IOVS, May 2012, Vol. 53, No. 6 KLEIP Deficiency in Corneal Neovascular Dystrophy 3261 mice developed progressively a corneal dystrophy due to epithelial fragility, which was induced mainly by mechanical injuries of the cornea. Therefore, KLEIP-deficient mice represent a unique genetic model to study onset and progression of corneal damages in mice. METHODS Generation and Genotyping of KLEIP-/- Mice The 129SvEv embryonic stem cell clone XF202 (BayGenomics), carrying the b-geo (beta galactosidases and neomycin resistance) encoding vector pGT2Lxf in the KLEIP locus, was injected into C57/BL6 blastocytes, crossed, and maintained in C57/BL6 Ola mice. Currently, mice are in the F10 generation and named as B6.129-KLEIPtm/Mhm.For genotyping, three primers were used, namely primer S1, which binds in intron 2 of genomic KLEIP; primer A1, which binds in the gene trap vector, and primer A2, which binds in exon 3 of KLEIP. Primer pair S1 and A2 generated the wild type band of 1349 base pair (bp) length, while primer pair S1 and A1 generated the transgenic signal of 591 bp length. Expression of lacZ was analyzed using primer pair L1 and L2 (Supplemental Fig. 1, http://www.iovs.org/lookup/suppl/doi:10.1167/ iovs.12-9676/-/DCSupplemental). For primer sequences see below. Mice were kept under specific pathogen-free conditions according to the animal facility regulations of the Medical Faculty Mannheim, Heidelberg University. All animal experiments were approved by the Regierungspr¨asidium Karlsruhe (protocol numbers 35-9185.83, 35- 9185.81/G-82/11, and I-07/03), and are in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Antibodies and Histologic Reagents The following antibodies were used for the study: anti-mouse CD31, clone MEC 13.3 (BD Pharmingen, Heidelberg, Germany); anti-mouse Endomucin, clone V.1A7, and anti-mouse keratin-12 (Santa Cruz Biotechnology, Heidelberg, Germany); anti-mouse E-cadherin, clone ECCD-2 (Invitrogen, Darmstadt, Germany); anti-mouse LYVE-1 (RELIA- Tech, Wolfenbuttel,¨ Germany); anti-mouse F4/80, clone CI: A3-1, and donkey-anti-rabbit FITC (Dianova, Hamburg, Germany); anti-mouse keratin-1, anti-mouse keratin-14, and anti-mouse loricrin (Covance, Munchen,¨ Germany); anti-human Ki67 (Novocastra, Wetzlar, Ger- many); goat-anti-rat Alexa 546 and goat-anti-rabbit Alexa 488 (Molecular Probes, Darmstadt, Germany); HRP-conjugated antibodies and ABC-kit (VECTOR Laboratories, Dossenheim, Germany); and DAPI, HE staining solution, Sudan black B solution, Trichrome Stain (Masson) Kit, and anti-human SMA, clone 1A4 (Sigma-Aldrich, Munchen,¨ Germany). Histochemistry Eyes from KLEIPþ/þ and KLEIP-/- mice were enucleated, and corneas were isolated via cutting around the corneoscleral limbal ring. Eyelids -/- were dissected using a scalpel. Tissues were fixed in 4% formaldehyde FIGURE 1. KLEIP mice developed a corneal dystrophy. (A) Corneal dystrophy phenotype in a KLEIP-/- mouse as indicated by a corneal (PFA) or in Zn-fixative overnight at 48C, or immediately frozen in liquid opacity.
Load more

Recommended publications
  • Understanding Corneal Blindness
    Understanding Corneal Blindness The cornea copes very well with minor injuries or abrasions. If the highly sensitive cornea is scratched, healthy cells slide over quickly and patch the injury before infection occurs and vision is affected. If the scratch penetrates the cornea more deeply, however, the healing process will take longer, at times resulting in greater pain, blurred vision, tearing, redness, and extreme sensitivity to light. These symptoms require professional treatment. Deeper scratches can also cause corneal scarring, resulting in a haze on the cornea that can greatly impair vision. In this case, a corneal transplant may be needed. Corneal Diseases and Disorders that May Require a Transplant Corneal Infections. Sometimes the cornea is damaged after a foreign object has penetrated the tissue, such as from a poke in the eye. At other times, bacteria or fungi from a contaminated contact lens can pass into the cornea. Situations like these can cause painful inflammation and corneal infections called keratitis. These infections can reduce visual clarity, produce corneal discharges, and perhaps erode the cornea. Corneal infections can also lead to corneal scarring, which can impair vision and may require a corneal transplant. Fuchs' Dystrophy. Fuchs' Dystrophy occurs when endothelial cells gradually deteriorate without any apparent reason. As more endothelial cells are lost over the years, the endothelium becomes less efficient at pumping water out of the stroma (the middle layers of the cornea). This causes the cornea to swell and distort vision. Eventually, the epithelium also takes on water, resulting in pain and severe visual impairment. Epithelial swelling damages vision by changing the cornea's normal curvature, and causing a sightimpairing haze to appear in the tissue.
    [Show full text]
  • Peripheral Hypertrophic Subepithelial Corneal Degeneration Presenting
    Eye (2015) 29, 88–97 & 2015 Macmillan Publishers Limited All rights reserved 0950-222X/15 www.nature.com/eye 1,2 3 4 CLINICAL STUDY Peripheral MSchargus , C Kusserow ,USchlo¨ tzer-Schrehardt , C Hofmann-Rummelt4, G Schlunck1 hypertrophic and G Geerling1,5 subepithelial corneal degeneration presenting with bilateral nasal and temporal corneal changes Abstract 1 Department of Purpose To characterise the history, clinical transmission electron microscopy showed Ophthalmology, University of Wuerzburg, Wuerzburg, and histopathological features of patients histological features that are similar to Germany with bilateral nasal and temporal peripheral Salzmann’s corneal changes without any hypertrophic subepithelial corneal inflammation. We hypothesise that light 2Department of degeneration in a German population. exposure and a localised limbal insufficiency Ophthalmology, University Methods A detailed ophthalmological and could be involved in the pathogenesis. of Bochum, Bochum, dermatological history and clinical findings Eye (2015) 29, 88–97; doi:10.1038/eye.2014.236; Germany were recorded of nine patients with bilateral published online 3 October 2014 3Department of simultaneous nasal and temporal peripheral Ophthalmology, University corneal degeneration from two centers in of Luebeck, Lu¨ beck, Germany. Excised tissues were studied by Introduction Germany histopathology, immunohistochemistry, and transmission electron microscopy. Salzmann’s nodules (SN) are subepithelial, 4 Department of Results Foreign body sensation and need elevated bluish-white corneal opacities of non- Ophthalmology, University inflammatory origin, with a specific peripheral of Erlangen-Nuernberg, of artificial tear substitutes were the only 1–7 Erlangen, Germany symptoms reported regularly. Schirmer’s and circular pattern. What has been termed Jones-test were normal in all, but fluorescein Salzmann’s degeneration is predominantly 5Department of break-up time of 410 s was found in five eyes unilateral, presenting at any time in life with Ophthalmology, University of four patients.
    [Show full text]
  • Its Not Just Dry Eye NCOS2021
    5/31/21 DISCLOSURES CORNEA ENDOTHELIOPATHIES NOPE, THAT’S NOT JUST DRY EYE: PRIMARY SECONDARY OTHER CORNEAL DISEASES • Corneal guttata • Contact lens wear • Fuchs dystrophy • Surgical procedures • Posterior Polymorphous Dystrophy (PPD) • Age related Cecelia Koetting, OD FAAO • Congenital hereditary endothelial dystrophy • Iatrogenic (im munodeficiency) (CHED) • Glaucoma induced Virginia Eye Consultants • Iridocorneal endothelial syndrome (ICE) • Ocular inflammation Norfolk, VA 1 2 3 OTHER CORNEAL CORNEAL FUNCTION • Keratoconus • Central cloudy dystrophy of Francois • Pellucid marginal degeneration • Thiel-Behnke corneal dystrophy • Shields the eye from germs, dust, other harmful matter • Lattice Dystrophy • Ocular Bullous pemphigoid WHY IS THE CORNEA IMPORTANT? • Contributes between 65-75% refracting power to the eye • Recurrent corneal erosion (RCE) • SJS • Filters out some of the most harmful UV wavelengths • Granular corneal dystrophy • Band Keratopathy • Reis-Bucklers corneal dystrophy • Corneal ulcer • Schnyder corneal dystrophy • HSV/HZO • Congenital Stromal corneal dystrophy • Pterygium • Fleck corneal dystrophy • Burns/Scars • Macular corneal dystrophy • Perforations • Posterior amorphous corneal dystrophy • Vascularized cornea 4 5 6 CORNEAL ANATOMY CORNEA Epithelium Bowmans Layer • Cornea is a transparent, avascular structure consisting of 6 layers • A- Anterior Epithelium: non-keratinized stratified squamous epithelium; cells migrate from BRIEF ANATOMY REVIEW Stroma basal layer upward and periphery to center • B- Bowmans Membrane:
    [Show full text]
  • The Latest in Corneal Degenerations and Dystrophies Corneal
    5/20/2014 Epithelial (Anterior) Basement Membrane CORNEAL DEGENERATION Dystrophy (EBMD or ABMD) • Non-familial, late onset • Easy to overlook: The Latest In Corneal • Asymmetric, unilateral, central or peripheral – typically bilateral though often asymmetric, Degenerations and Dystrophies • Changes to the tissue caused by inflammation, – females>males, age, or systemic disease. – often first diagnosed b/w ages of 40-70 Blair B Lonsberry, MS, OD, MEd., FAAO Characterized by a deposition of material, a Diplomate, American Board of Optometry • Clinic Director and Professor thinning of tissue, or vascularization Pacific University College of Optometry Portland, OR [email protected] Epithelial (Anterior) Basement Membrane Epithelial (Anterior) Basement Membrane Dystrophy (EBMD or ABMD) Dystrophy (EBMD or ABMD) • Most common • Primary features of this “dystrophy” are: findings are: – abnormal corneal epithelial regeneration and – chalky patches, maturation, – intraepithelial – abnormal basement membrane microcysts, and • Often considered the most common dystrophy, – fine lines (or any but may actually be an age-related degeneration. combination) in the central 2/3rd of CORNEAL DYSTROPHIES – large number of patients with this condition, cornea – increasing prevalence with increasing age, and – its late onset support a degeneration vs. dystrophy. 2 2 8 Epithelial (Anterior) Basement Membrane Epithelial (Anterior) Basement Membrane Corneal Dystrophies Dystrophy (EBMD or ABMD) Dystrophy (EBMD or ABMD) • Group of corneal diseases that are:
    [Show full text]
  • 75 2. INTRODUCTION Triple-Negative Breast Cancer (TNBC)
    [Frontiers in Bioscience, Scholar, 11, 75-88, March 1, 2019] The persisting puzzle of racial disparity in triple negative breast cancer: looking through a new lens Chakravarthy Garlapati1, Shriya Joshi1, Bikram Sahoo1, Shobhna Kapoor2, Ritu Aneja1 1Department of Biology, Georgia State University, Atlanta, GA, USA, 2Department of Chemistry, Indian Institute of Technology Bombay, Powai, India TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Dissecting the TNBC racially disparate burden 3.1. Does race influence TNBC onset and progression? 3.2. Tumor microenvironment in TNBC and racial disparity 3.3. Differential gene signatures and pathways in racially distinct TNBC 3.4. Our Perspective: Looking racial disparity through a new lens 4. Conclusion 5. Acknowledgement 6. References 1. ABSTRACT 2. INTRODUCTION Triple-negative breast cancer (TNBC) Triple-negative breast cancer (TNBC), is characterized by the absence of estrogen a subtype of breast cancer (BC), accounts for and progesterone receptors and absence 15-20% of all BC diagnoses in the US. It has of amplification of human epidermal growth been recognized that women of African descent factor receptor (HER2). This disease has no are twice as likely to develop TNBC than approved treatment with a poor prognosis women of European descent (1). As the name particularly in African-American (AA) as foretells, TNBCs lack estrogen, progesterone, compared to European-American (EA) and human epidermal growth factor receptors. patients. Gene ontology analysis showed Unfortunately, TNBCs are defined by what they specific gene pathways that are differentially “lack” rather than what they “have” and thus this regulated and gene signatures that are negative nomenclature provides no actionable differentially expressed in AA as compared to information on “druggable” targets.
    [Show full text]
  • Proteomic Expression Profile in Human Temporomandibular Joint
    diagnostics Article Proteomic Expression Profile in Human Temporomandibular Joint Dysfunction Andrea Duarte Doetzer 1,*, Roberto Hirochi Herai 1 , Marília Afonso Rabelo Buzalaf 2 and Paula Cristina Trevilatto 1 1 Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba 80215-901, Brazil; [email protected] (R.H.H.); [email protected] (P.C.T.) 2 Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru 17012-901, Brazil; [email protected] * Correspondence: [email protected]; Tel.: +55-41-991-864-747 Abstract: Temporomandibular joint dysfunction (TMD) is a multifactorial condition that impairs human’s health and quality of life. Its etiology is still a challenge due to its complex development and the great number of different conditions it comprises. One of the most common forms of TMD is anterior disc displacement without reduction (DDWoR) and other TMDs with distinct origins are condylar hyperplasia (CH) and mandibular dislocation (MD). Thus, the aim of this study is to identify the protein expression profile of synovial fluid and the temporomandibular joint disc of patients diagnosed with DDWoR, CH and MD. Synovial fluid and a fraction of the temporomandibular joint disc were collected from nine patients diagnosed with DDWoR (n = 3), CH (n = 4) and MD (n = 2). Samples were subjected to label-free nLC-MS/MS for proteomic data extraction, and then bioinformatics analysis were conducted for protein identification and functional annotation. The three Citation: Doetzer, A.D.; Herai, R.H.; TMD conditions showed different protein expression profiles, and novel proteins were identified Buzalaf, M.A.R.; Trevilatto, P.C.
    [Show full text]
  • Keratin 12-Deficient Mice Have Fragile Corneal Epithelia
    Keratin 12-Deficient Mice Have Fragile Corneal Epithelia Winston W.—Y. Kao,* Chia-YangLiu,* Richard L. Converse,* Atsushi Shiraishi* Candace W.-C. Kao,* Masamichi Ishizaki* Thomas Doetschman,^ and John Duffy-f Purpose. Expression of the K3-K12 keratin pair characterizes the corneal epithelial differentia- tion. To elucidate the role of keratin 12 in the maintenance of corneal epithelium integrity, the authors bred mice deficient in keratin 12 by gene-targeting techniques. Methods. One allele of murine Krtl.12 gene was ablated in the embryonic stem cell line, E14.1, by homologous recombination with a DNA construct in which the DNA element between intron 2 and exon 8 of the keratin 12 gene was replaced by a neo-gene. The homologous recombinant embryonic stem cells were injected to mouse blastocysts, and germ lines of chimeras were obtained. The corneas of heterozygous and homozygous mice were characterized by clinical observations using stereomicroscopy, histology with light and electron microscopy, Western immunoblot analysis, immunohistochemistry, in situ hybridization, and Northern hybridization. Results. The heterozygous mice (+/—) one allele of the Krtl.12 gene appear normal and do not develop any clinical manifestations (e.g., corneal epithelial defects). Homozygous mice (—/—) develop normally and suffer mild corneal epithelial erosion. Their corneal epithelia are fragile and can be removed by gentle rubbing of the eyes or brushing with a Microsponge. The corneal epithelium of the homozygote (—/—) does not express keratin 12 as judged by immunohistochemis- try, Western immunoblot analysis with epitope-specific anti-keratin 12 antibodies, Nordiern hybrid- ization with 32P-labeled keratin 12 cDNA, and in situ hybridization with an anti-sense keratin 12 riboprobe.
    [Show full text]
  • Bilateral Cataract Surgery in Posterior Polymorphous Corneal Dystrophy
    J Clin Case Rep Trials 2018 Journal of Volume 1: 1 Clinical Case Reports and Trials Bilateral Cataract Surgery in Posterior Polymorphous Corneal Dystrophy Taha Ayyildiz1* 1Department of Ophthalmology, Ahi Evran University, Kırsehir, Turkey Abstract Article Information Posterior polymorphous corneal dystrophy (PPCD) is an autosomal Article Type: Case Report dominant corneal dystrophy and usually non-progressive which is Article Number: JCCRT101 characterized by metaplasia and excessive growth of the corneal Received Date: 06th-March -2018 endothelium and Descemet’s membrane defects. Biomicroscopic slit Accepted Date: 14th-April -2018 Published Date: 19th-April -2018 lesions are observed. The patients are usually asymptomatic corneal edemalamp examination was observed shows in some isolated advanced or confluent cases. The vesicles evaluation and ofbands 38-year- like *Corresponding author: Dr. Taha Ayyildiz, Department old male patient who admitted to our clinic and it was observed every of Ophthalmology, Ahi Evran University, Kırsehir, Turkey. 2 cornea PPCD that the accompanying dense nuclear sclerosis cataracts. Tel: +90-386-280-42-00; E-mail: [email protected] In this study, we aimed to share the results of uncomplicated cataract surgery. Citation: Ayyildiz T (2018) Bilateral Cataract Surgery in Posterior Polymorphous Corneal Dystrophy. J Clin Case Keywords: Rep Trials. Vol: 1, Issu: 1 (01-03). dystrophy. Phacoemulsification, Cataract, Posterior polymorphous Copyright: © 2018 Ayyildiz T. This is an open-access Introductıon article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the Koeppé in 1916 withwide corneal and anterior segment anomaly [1]. It original author and source are credited.
    [Show full text]
  • Familial Pathologic Myopia, Corneal Dystrophy, and Deafness: a New Syndrome
    Familial Pathologic Myopia, Corneal Dystrophy, and Deafness: A New Syndrome Emin Kurt*, Abdullah Günen†, Yılmaz Sadıkog˘ lu†, Faruk Öztürk*, Serdar Tarhan‡, Refik Ali Sarı§, Tevhide Fıstıkʈ and Zeki Arı¶ Departments of *Ophthalmology, †Otorhinolaryngology, ‡Radiology, §Internal Medicine, ʈMedical Genetics, and ¶Biochemistry, School of Medicine, University of Celal Bayar, Manisa, Turkey Background: Numerous syndromes with myopia and hearing loss have been described up to now. We present a family with pathologic myopia, corneal dystrophy, and deafness distinct from these syndromes. Cases: Ten patients in the same Turkish family were evaluated by ophthalmologic, audio- logic, physical, radiologic, genetic, serologic, and biochemical examinations. Observations: Ophthalmic examination indicated that all the cases had myopia, 7 of them had pathologic myopia, 1 had intermediate, and 2 had mild. Four of the patients with patho- logic myopia had corneal dystrophy that was bilaterally manifest as white opacities in the posterior stroma near Descemet’s membrane in an axial distribution; 1 of these 4 patients also had a tilted disc. Otolaryngologic examination revealed conductive hearing loss in 3 cases, mixed hearing loss in 2, and sensorineural hearing loss in 1. The results of karyotypic analyses of all cases were normal. The pedigree analysis showed the disease was inherited through successive generations as an autosomal dominant trait. The results of biochemical, serologic, and radiologic investigations were normal. The same pathophysiologic process in all cases seemed to account for the myopia, the corneal dystrophy and the deafness. Conclusions: To our knowledge, this type of case has not been reported in the literature. Therefore, we named this syndrome “familial pathologic myopia, corneal dystrophy and deafness.” Jpn J Ophthalmol 2001;45:612–617 ©2001 Japanese Ophthalmological Society Key Words: Corneal dystrophy, hearing loss, pathologic myopia, tilted disc, syndrome.
    [Show full text]
  • Avellino Corneal Dystrophy After LASIK
    Avellino Corneal Dystrophy after LASIK Roo Min Jun, MD,1,4 Hungwon Tchah, MD,2 Tae-im Kim, MD,2 R. Doyle Stulting, MD, PhD,3 Seung Eun Jung, MS,4,6 Kyoung Yul Seo, MD,4 Dong Ho Lee, MD,5 Eung Kweon Kim, MD, PhD4,6 Objective: To report cases of Avellino corneal dystrophy (ACD) exacerbated by LASIK for myopia. Design: Retrospective, noncomparative, interventional case series and review of the literature. Participants: Seven patients. Intervention: Six patients with exacerbation of granular corneal deposits after LASIK were examined for TGFBI mutations by polymerase chain reaction sequencing of DNA. One previously reported patient who was heterozygous for the ACD gene was followed up for 16 months after mechanical removal of granular deposits from the interface after LASIK. Main Outcome Measures: Slit-lamp examination, visual acuity, manifest refraction, and DNA sequencing analysis. Results: All patients were heterozygous for the Avellino dystrophy gene. Corneal opacities appeared 12 months or more after LASIK. Best spectacle-corrected visual acuity decreased as the number and density of the opacities increased. One patient underwent mechanical removal of granules from the interface and had a severe recurrence within 16 months. Another patient had removal of the granules from the interface with PTK, followed by treatment with topical mitomycin C. In this patient, the cornea has remained relatively clear for 6 months. Conclusions: Laser in situ keratomileusis increases the deposition of visually significant corneal opacities and is contraindicated in patients with ACD. Mechanical removal of the material from the interface does not prevent further visually significant deposits. Mitomycin C treatment, in conjunction with surgical removal of opacities, may be an effective treatment.
    [Show full text]
  • The Outcome of Penetrating Keratoplasty for Corneal Scarring
    ORIGINAL ARTICLE The outcome of penetrating keratoplasty for corneal scarring due to herpes simplex keratitis O resultado da ceratoplastia penetrante para cicatriz de córnea consequente à ceratite por herpes simplex YESIM ALTay1, SEMA TAMER1, ABDULLAH SENCER Kaya1, OZGUR BALTA1, AYSE BURCU1, FIRDEVS ORNEK1 ABSTRACT RESUMO Purpose: To determine the outcomes of penetrating keratoplasty (PK) for treatment Objetivo: Determinar os resultados da ceratoplastia penetrante (PK) para o trata- of corneal scarring caused by Herpes simplex virus (HSV) keratitis, and whether mento da cicatriz da córnea consequente à ceratite por Herpes simplex vírus (HSV), the corneal scar type affects treatment outcome. e se o tipo de cicatriz na córnea afeta o resultado cirúrgico. Methods: A retrospective analysis of patients who underwent PK for HSV-related Métodos: Foi realizada análise retrospectiva dos pacientes, submetidos à PK para corneal scarring between January 2008 and July 2011 was performed. The patients a cicatriz da córnea relacionados com o HSV entre janeiro de 2008 e julho de 2011. were categorized into two groups. Group 1 consisted of patients with a quiescent Os pacientes foram divididos em dois grupos. Grupo 1 consistiu de pacientes que herpetic corneal scar and group 2 consisted of patients who developed a corneal tiveram cicatriz corneana herpética quiescente e grupo 2 consistiu de pacientes que descemetocele or perforation secondary to persistent epithelial defects with no desenvolveram descemetocele ou perfuração córnea secundária a defeitos epiteliais active stromal inflammation. The mean follow-up was 21.30 ± 14.59 months. The persistentes sem inflamação estromal ativa. O seguimento médio foi de 21,30 ± 14,59 main parameters evaluated were recurrence of herpetic keratitis, graft rejection, meses.
    [Show full text]
  • Coincident Pellucid Marginal Degeneration and Fuchs’ Endothelial Dystrophy 1James Mckelvie, 2Cameron Andrew Mclintock, 3Samer Hamada
    IJKECD James McKelvie et al. 10.5005/jp-journals-10025-1170 CASE REPORT Coincident Pellucid Marginal Degeneration and Fuchs’ Endothelial Dystrophy 1James McKelvie, 2Cameron Andrew McLintock, 3Samer Hamada ABSTRACT BACKGROUND Aim: We report a rare case of coincident pellucid marginal Pellucid marginal degeneration (PMD) is a rare, bilateral, degeneration and Fuchs’ endothelial dystrophy. non-inflammatory corneal ectatic disorder characterized 1 Background: As far as the authors are aware there have been by a band of inferior corneal thinning. PMD has a 3:1 male no previous reports of this combination of corneal disorders predominance and typically presents between the ages of in the same patient. 20–50 years with declining vision, irregular astigmatism, and inferior steepening and thinning noted on corneal Case description: A 45-year-old woman presented with tomography.2-4 Fuchs’ endothelial corneal dystrophy (FECD) progressive pellucid marginal degeneration and Fuchs’ endo- thelial dystrophy. Progressive changes in corneal topography is the most common corneal dystrophy and the most common 5 and specular microscopy imaging have been documented dystrophy-related indication for corneal transplantation. over 13 years since presentation. Declining vision has been FECD is characterized by progressive loss of corneal endothe- successfully managed in this patient, to date, with serial cres- lial cells, a formation of guttae and decreased vision typically centic corneal wedge excision biopsies to maintain acceptable associated with corneal edema.6 In contrast to PMD, FECD spectacle-corrected visual acuity. has a 2.5–3:1 female predominance and presentation is typi- Conclusion: This rare combination of corneal disorders pre- cally either as an early onset subtype in the third decade, or 5 sents an interesting and unique challenge for surgical manage- a late onset subtype in the fifth decade of life.
    [Show full text]