title: Proteomic profiling of inflammatory signaling molecules in the tears of patients on chronic glaucoma medication.
abstract: OBJECTIVE
  To identify the tear proteins associated with the long-term use of glaucoma medication by using proteomic analysis and to compare these proteins to those previously reported in primary dry eye disease.
  
  
  METHODS
  Eighteen patients treated with topical antiglaucoma medications and 10 normal age-matched subjects with no prior topical treatment were recruited for the study. Tears were collected by using Schirmer's strip and analyzed by iTRAQ (isobaric tag for relative and absolute quantitation) for tear proteins by mass spectrometry. Conjunctival samples were collected and RNA expression determined by PCR.
  
  
  RESULTS
  Of the 124 identified tear proteins (99% confidence, ProtScore ≥ 2.0), we found that the tear levels of S100-A8, S100-A9, mammaglobin B, and 14-3-3 ζ/δ were significantly increased in the medicated group compared with levels in the nonmedicated group (P < 0.05). For S100-A9, mammaglobin B, and 14-3-3 ζ/δ, use of topical medication for less than 1 year did not reach statistical significance compared with that in the nonmedicated group. Eyes on topical medication for less than 1 year showed a decrease in proline-rich 4 protein tear level (P = 0.0049) compared to nonmedicated group. The tear proteins detected in the medicated group differed from those in the primary dry eye group.
  
  
  CONCLUSIONS
  Treatment with topical antiglaucoma medications for longer than 1 year may start to induce ocular surface inflammation. The inflammatory tear protein profile present in chronically medicated glaucomatous eyes appears to be different from that found in primary dry eye. Identification of tear proteins specific to medicated glaucomatous eyes will help to specifically develop targeted screening modalities and therapeutic agents different from current conventional dry eye management.
authors.affiliation: Singapore Eye Research Institute, Singapore. tina.wong.t.l@snec.com.sg
authors.forename: Tina T
authors.initials: TT
authors.lastname: Wong
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Louis
authors.initials: L
authors.lastname: Tong
authors.forename: Shao Zhen
authors.initials: SZ
authors.lastname: Zhao
authors.forename: Xiao Rong
authors.initials: XR
authors.lastname: Li
authors.forename: Shang Juan
authors.initials: SJ
authors.lastname: Yu
authors.forename: Siew Kwan
authors.initials: SK
authors.lastname: Koh
authors.forename: Roger W
authors.initials: RW
authors.lastname: Beuerman
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D015153:Blotting, Western; D015352:Dry Eye Syndromes / Q000235:genetics; D020224:Expressed Sequence Tags; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D005901:Glaucoma / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments; D040081:Protein Array Analysis; D040901:Proteomics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D013666:Tears / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D005136:Eye Proteins; D010446:Peptide Fragments; C042434:tear proteins