Altered secretion of a TIGR/MYOC mutant lacking the olfactomedin domain

Biochim Biophys Acta. 2000 Nov 15;1502(3):447-60. doi: 10.1016/s0925-4439(00)00068-5.


TIGR/MYOC, a novel 504 amino acids (aa) protein of unknown function, has recently been linked to glaucoma. The protein is both intra- and extracellular and most known mutations map to its C-terminus, an olfactomedin-like domain. To investigate the properties of a TIGR/MYOC peptide lacking this important domain, we constructed a replication-deficient adenovirus with the first 344 aa and over-expressed the truncated protein in primary human trabecular meshwork cells and perfused human anterior segment cultures. The truncated mutant contains the entire N-terminus plus 98 aa of the olfactomedin-like domain. We found that the delivered truncated mutant accumulates inside the cell, reduces secretion of endogenous TIGR/MYOC and induces an increase in outflow facility at 48 h post-infection. Based on these findings, we hypothesize that TIGR/MYOC might have a dual role in trabecular meshwork function. This dual role might be that of an intracellular modulator of vesicular transport as well as that of a secreted protein involved in extracellular matrix conformation. Both functions could have a direct effect in maintaining aqueous humor outflow facility.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / chemistry
  • Adenoviridae / genetics
  • Amino Acid Sequence
  • Anterior Eye Segment / drug effects
  • Anterior Eye Segment / metabolism*
  • Biological Transport
  • Blotting, Northern
  • Blotting, Western
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Cytoskeletal Proteins
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / pharmacology
  • Eye Proteins / biosynthesis
  • Eye Proteins / genetics*
  • Eye Proteins / pharmacology
  • Glaucoma / metabolism*
  • Glycoproteins / biosynthesis
  • Glycoproteins / chemistry
  • Glycoproteins / genetics*
  • Glycoproteins / pharmacology
  • Humans
  • Immunohistochemistry
  • Intraocular Pressure
  • Molecular Sequence Data
  • Mutation
  • Organ Culture Techniques
  • Perfusion
  • Recombinant Proteins / pharmacology
  • Rheology
  • Trabecular Meshwork / metabolism


  • Cytoskeletal Proteins
  • Extracellular Matrix Proteins
  • Eye Proteins
  • Glycoproteins
  • Recombinant Proteins
  • olfactomedin
  • trabecular meshwork-induced glucocorticoid response protein