title: Exfoliation syndrome: assembling the puzzle pieces.
abstract: OBJECTIVE
  To summarize various topics and the cutting edge approaches to refine XFS pathogenesis that were discussed at the 21st annual Glaucoma Foundation Think Tank meeting in New York City, Sept. 19-20, 2014.
  
  
  METHODS
  The highlights of three categories of talks on cutting edge research in the field were summarized.
  
  
  RESULTS
  Exfoliation syndrome (XFS) is a systemic disorder with a substantial ocular burden, including high rates of cataract, cataract surgery complications, glaucoma and retinal vein occlusion. New information about XFS is akin to puzzle pieces that do not quite join together to reveal a clear picture regarding how exfoliation material (XFM) forms.
  
  
  CONCLUSIONS
  Meeting participants concluded that it is unclear how the mild homocysteinemia seen in XFS might contribute to the disarrayed extracellular aggregates characteristic of this syndrome. Lysyl oxidase-like 1 (LOXL1) variants are unequivocally genetic risk factors for XFS but exactly how these variants contribute to the assembly of exfoliation material (XFM) remains unclear. Variants in a new genomic region, CACNA1A associated with XFS, may alter calcium concentrations at the cell surface and facilitate XFM formation but much more work is needed before we can place this new finding in proper context. It is hoped that various animal model and ex vivo systems will emerge that will allow for proper assembly of the puzzle pieces into a coherent picture of XFS pathogenesis. A clear understanding of XFS pathogenesis may lead to 'upstream solutions' to reduce the ocular morbidity produced by XFS.
authors.affiliation: Department of Ophthalmology, Mass Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.|Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Louis R
authors.initials: LR
authors.lastname: Pasquale
authors.affiliation: Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Terete
authors.initials: T
authors.lastname: Borrás
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Fingert
authors.affiliation: Department of Ophthalmology, Mass Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
authors.affiliation: Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York City, New York, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ritch
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D017889:Exfoliation Syndrome / Q000209:etiology* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005902:Glaucoma, Open-Angle / Q000209:etiology* / Q000378:metabolism; D006710:Homocysteine / Q000502:physiology; D006801:Humans; D020864:Calcium Channels, N-Type
chemical_list: D000594:Amino Acid Oxidoreductases; D002118:Calcium; D015220:Calcium Channels; D016326:Extracellular Matrix Proteins; D006710:Homocysteine; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C445313:LOXL1 protein, human
keywords: CACNA1A; LOXL1; animal models; exfoliation syndrome; homocysteine