title: Comparison of telomere length and association with progenitor cell markers in lacrimal gland between Sjögren syndrome and non-Sjögren syndrome dry eye patients.
abstract: OBJECTIVE
  Indicators of aging such as disruption of telomeric function due to shortening may be more frequent in dysfunctional lacrimal gland. The aims of this study were to 1) determine the viability of quantitative fluorescence in situ hybridization of telomeres (telo-FISH) for the assessment of telomere length in lacrimal gland in Sjögren and non- Sjögren syndrome patients; and 2) investigate the relationship between progenitor cell markers and telomere length in both groups.
  
  
  METHODS
  Quantitative fluorescence in situ hybridization with a peptide nucleic acid probe complementary to the telomere repeat sequence was performed on frozen sections from human lacrimal gland tissues. The mean fluorescence intensity of telomere spots was automatically quantified by image analysis as relative telomere length in lacrimal gland epithelial cells. Immunostaining for p63, nucleostemin, ATP-binding cassette, sub-family G, member 2 (ABCG2), and nestin was also performed.
  
  
  RESULTS
  Telomere intensity in the Sjögren syndrome group (6,785.0±455) was significantly lower than that in the non-Sjögren syndrome group (7,494.7±477; p=0.02). Among the samples from the non-Sjögren syndrome group, immunostaining revealed that p63 was expressed in 1-3 acinar cells in each acinar unit and continuously in the basal layer of duct cells. In contrast, in the Sjögren syndrome group, p63 and nucleostemin showed a lower level of expression. ABCG2 was expressed in acinar cells in both sjogren and non-Sjogren syndrome.
  
  
  CONCLUSIONS
  The results of this study indicate that 1) telo-FISH is a viable method of assessing telomere length in lacrimal gland, and 2) telomere length in Sjögren syndrome is shorter and associated with lower levels of expression of p63 and nucleostemin than in non-Sjögren syndrome.
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Kawashima
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawakita
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Maida
authors.forename: Mizuka
authors.initials: M
authors.lastname: Kamoi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Shigeto
authors.initials: S
authors.lastname: Shimmura
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Masutomi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics; D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007765:Lacrimal Apparatus / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000473:pathology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014985:Xerophthalmia / Q000235:genetics* / Q000473:pathology
chemical_list: D015415:Biomarkers; C081876:CKAP4 protein, human; C469949:GNL3 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D019204:GTP-Binding Proteins