Genetic and genomic perspective to understand the molecular pathogenesis of keratoconus.
Nallathambi Jeyabalan,Rohit Shetty,Anuprita Ghosh,Venkata Ramana Anandula,Arkasubhra Ghosh,Govindasamy Kumaramanickavel +5 more
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TLDR
The focus of this review is to provide a concise update on the current knowledge of the genetic basis of KC and genomic approaches to understand the disease pathogenesis.Abstract:
Keratoconus (KC; Mendelian Inheritance in Man (OMIM) 14830) is a bilateral, progressive corneal defect affecting all ethnic groups around the world. It is the leading cause of corneal transplantation. The age of onset is at puberty, and the disorder is progressive until the 3 rd -4 th decade of life when it usually arrests. It is one of the major ocular problems with significant social and economic impacts as the disease affects young generation. Although genetic and environmental factors are associated with KC, but the precise etiology is still elusive. Results from complex segregation analysis suggests that genetic abnormalities may play an essential role in the susceptibility to KC. Due to genetic heterogeneity, a recent study revealed 17 different genomic loci identified in KC families by linkage mapping in various populations. The focus of this review is to provide a concise update on the current knowledge of the genetic basis of KC and genomic approaches to understand the disease pathogenesis.read more
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Journal Article
VSX1: A gene for Posterior Polymorphous Dystrophy and Keratoconus
Elise Heon,Kelly K. Kopp,Rod Bremner,Daniel B. Rootman,RL Chow,K Dorval,Andrea L Vincent,C.A. Westall,John E. Sutphin,Edwin M. Stone +9 more
TL;DR: This article identified mutations in the VSX1 homeobox gene for two distinct inherited corneal dystrophies; posterior polymorphous dystrophy (PPD) and keratoconus.
Journal ArticleDOI
Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A.
Rohit Shetty,Anuprita Ghosh,Rayne R. Lim,Murali Subramani,Krina Mihir,A. R. Reshma,Ashwini Ranganath,Sriharsha Nagaraj,Rudy M.M.A. Nuijts,Roger W. Beuerman,Reshma Shetty,Debashish Das,Shyam S. Chaurasia,Abhijit Sinha-Roy,Arkasubhra Ghosh +14 more
TL;DR: The data indicate that corneal epithelium contributes to elevated MMP9 and inflammatory cytokine expression in tears of KC patients, and CyA might be a novel treatment strategy in KC patients but requires additional evaluation in larger cohorts.
Journal ArticleDOI
Differential Molecular Expression of Extracellular Matrix and Inflammatory Genes at the Corneal Cone Apex Drives Focal Weakening in Keratoconus
Natasha Pahuja,Nimisha R Kumar,Rushad Shroff,Rohit Shetty,Rudy M.M.A. Nuijts,Anuprita Ghosh,Abhijit Sinha-Roy,Shyam S. Chaurasia,Rajiv R. Mohan,Arkasubhra Ghosh +9 more
TL;DR: This study provides the first evidence that altered corneal epithelial and stromal expression of specific genes at the cornean cone apex drives focal structural weakness in keratoconus disease.
Journal Article
Attenuation of lysyl oxidase and collagen gene expression in keratoconus patient corneal epithelium corresponds to disease severity.
Rohit Shetty,Arunapriya Sathyanarayanamoorthy,Reshma Airody Ramachandra,Vishal Arora,Anuprita Ghosh,Purnima R Srivatsa,Natasha Pahuja,Rudy M.M.A. Nuijts,Abhijit Sinha-Roy,Rajiv R. Mohan,Arkasubhra Ghosh +10 more
TL;DR: The data demonstrates that the structural deformity of the KC cornea may be dependent on reduced expressions of collagens and LOX, as well as on MMP9 elevated by the corneal epithelium.
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Tear biomarkers for keratoconus
TL;DR: The importance of tear fluid as a source of biomarker for keratoconus is discussed and how advances in technology have helped map the complexity of tears and thereby molecular readouts of the disease are mapped.
References
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Keratoconus: A review
TL;DR: The definition, epidemiology, clinical features, classification, histopathology, aetiology and pathogenesis, and management and treatment strategies for keratoconus are reviewed.
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Epithelial Injury Induces Keratocyte Apoptosis: Hypothesized Role for the Interleukin-1 System in the Modulation of Corneal Tissue Organization and Wound Healing
Steven E. Wilson,Steven E. Wilson,Yu-Guang He,Jian Weng,Qian Li,Alasdair W. McDowall,Mark Vital,Eric L. Chwang +7 more
TL;DR: The epithelial/endothelial-stromal IL-1 system may mediate corneal tissue organization and responses to mechanical- and pathogen-induced injury through induction of keratocyte apoptosis and it is hypothesize that derangement's in this system may have a role in the pathogenesis of ker atoconus and other diseases of the cornea.