title: A role for epha2 in cell migration and refractive organization of the ocular lens.
abstract: OBJECTIVE
  The Epha2 receptor is a surprisingly abundant component of the membrane proteome of vertebrate lenses. In humans, genetic studies have linked mutations in EPHA2 to inherited and age-related forms of cataract, but the function of Epha2 in the lens is obscure. To gain insights into the role of Epha2, a comparative analysis of lenses from wild-type and Epha2(-/-) mice was performed.
  
  
  METHODS
  Epha2 distribution was examined using immunocytochemistry and Western blot analysis. Lens optical quality was assessed by laser refractometry. Confocal microscopy was used to analyze cellular phenotypes.
  
  
  RESULTS
  In wild-type lenses, Epha2 was expressed by lens epithelial cells and elongating fibers but was degraded during the later stages of fiber differentiation. Epha2-null lenses retained their transparency, but two key optical parameters, lens shape and internal composition, were compromised in Epha2(-/-) animals. Epha2-null lenses were smaller and more spherical than age-matched wild-type lenses, and laser refractometry revealed a significant decrease in refractive power of the outer cell layers of mutant lenses. In the absence of Epha2, fiber cells deviated from their normal course and terminated at sutures that were no longer centered on the optical axis. Patterning defects were also noted at the level of individual cells. Wild-type fiber cells had hexagonal cross-sectional profiles with membrane protrusions extending from the cell vertices. In contrast, Epha2(-/-) cells had irregular profiles, and protrusions extended from all membrane surfaces.
  
  
  CONCLUSIONS
  These studies indicate that Epha2 is not required for transparency but does play an indispensable role in the cytoarchitecture and refractive quality of the lens.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Shi
authors.forename: Alicia
authors.initials: A
authors.lastname: De Maria
authors.forename: Thomas
authors.initials: T
authors.lastname: Bennett
authors.forename: Alan
authors.initials: A
authors.lastname: Shiels
authors.forename: Steven
authors.initials: S
authors.lastname: Bassnett
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002386:Cataract / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007150:Immunohistochemistry; D007908:Lens, Crystalline / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D036104:Receptor, EphA2 / Q000096:biosynthesis*; D012029:Refraction, Ocular
chemical_list: D036104:Receptor, EphA2