Genetically increasing Myoc expression supports a necessary pathologic role of abnormal proteins in glaucoma

Mol Cell Biol. 2004 Oct;24(20):9019-25. doi: 10.1128/MCB.24.20.9019-9025.2004.


Despite the importance of MYOC for glaucoma, the protein's normal function(s) and the pathogenic mechanism(s) of MYOC mutations are not clear. Elevated intraocular pressure (IOP) and glaucoma are sometimes induced by corticosteroids, and corticosteroid use can result in substantially increased MYOC expression. It has been suggested, therefore, that steroid-induced MYOC protein levels cause steroid-induced glaucoma and that protein level-increasing mutations in MYOC contribute to glaucoma not associated with steroid use. A causative role of elevated MYOC levels in steroid-induced glaucoma is controversial, however, and it is not clear if elevated MYOC levels can result in IOP elevation. To directly test if increased levels of MYOC can cause IOP elevation and glaucoma, we generated bacterial artificial chromosome transgenic mice that overexpress Myoc at a level similar to that induced by corticosteroid use. These mice do not develop elevated IOP or glaucoma. Our present findings, along with the absence of glaucoma in mice completely lacking MYOC, show that changing the level of MYOC is not pathogenic (from absent to approximately 15 times normal). These findings suggest that noncoding sequence variants are unlikely to influence glaucoma and that disease pathogenesis in primary open-angle glaucoma patients is dependent upon the expression of abnormal mutant proteins. This work does not support a causative role for increased MYOC levels or the MYOC gene in steroid-induced glaucoma.

Publication types

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

MeSH terms

  • Adrenal Cortex Hormones / adverse effects
  • Adrenal Cortex Hormones / pharmacology
  • Adult
  • Animals
  • Cytoskeletal Proteins
  • Eye / anatomy & histology
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism*
  • Gene Expression Regulation* / drug effects
  • Glaucoma, Open-Angle / chemically induced
  • Glaucoma, Open-Angle / genetics
  • Glaucoma, Open-Angle / metabolism*
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism*
  • Humans
  • Intraocular Pressure / drug effects
  • Intraocular Pressure / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Optic Nerve / anatomy & histology
  • Optic Nerve / metabolism
  • Promoter Regions, Genetic
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / metabolism
  • Trabecular Meshwork / cytology
  • Trabecular Meshwork / metabolism


  • Adrenal Cortex Hormones
  • Cytoskeletal Proteins
  • Eye Proteins
  • Glycoproteins
  • trabecular meshwork-induced glucocorticoid response protein