title: LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis.
abstract: The cornea requires constant epithelial renewal to maintain clarity for appropriate vision. A subset of stem cells residing at the limbus is primarily responsible for maintaining corneal epithelium homeostasis. Trauma and disease may lead to stem cell deficiency and therapeutic targeting to replenish the stemness capacity has been stalled by the lack of reliable corneal epithelial stem cell markers. Here we identified the location of Lhx2 in mice (mLhx2) cornea and conjunctival tissue using an Lhx2eGFP reporter model and in human tissues (hLHX2). Lhx2 localized to the basal cells of central cornea, the conjunctiva and the entire limbal epithelium in humans and mice. To ascribe a functional role we generated Lhx2 conditional knockout (cKO) mice and the phenotypic effects in corneas were analyzed by slit lamp microscopy, in cell-based assays and in a model of corneal epithelium debridement. Immunodetection on corneal sections were used to visualize conjunctivalization, a sign of limbal barrier failure. Lhx2cKO mice produced reduced body hair and spontaneous epithelial defects in the cornea that included neovascularization, perforation with formation of scar tissue and opacification. Cell based assays showed that Lhx2cKO derived corneal epithelial cells have a significantly lower capacity to form colonies over time and delayed wound-healing recovery when compared to wildtype cells. Repeated corneal epithelial wounding resulted in decreased re-epithelialization and multiple cornea lesions in Lhx2cKO mice compared to normal recovery seen in wildtype mice. We conclude that Lhx2 is required for maintenance of the corneal epithelial cell compartment and the limbal barrier.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Sartaj
authors.affiliation: Margaret Dyson Vision Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Ru-ik
authors.initials: RI
authors.lastname: Chee
authors.affiliation: Margaret Dyson Vision Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Margaret Dyson Vision Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Pengxia
authors.initials: P
authors.lastname: Wan
authors.affiliation: Margaret Dyson Vision Research Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Aihong
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Guaiquil
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology Development, The Rockefeller University, New York, New York, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
authors.affiliation: Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Mark I
authors.initials: MI
authors.lastname: Rosenblatt
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D014157:Transcription Factors; D049452:Green Fluorescent Proteins
keywords: Cornea; LIM homeobox domain 2; Lhx2cKO; Limbus; Stem Cells; Wound healing