Subunits of the epithelial sodium channel family are differentially expressed in the retina of mice with ocular hypertension.
Glaucoma is a prevalent cause of blindness, resulting in the apoptotic death of retinal ganglion cells and optic nerve degeneration. The disease is often associated with elevated intraocular pressure, however, molecular mechanisms involved in ganglion cell death are poorly understood. To identify proteins contributing to this pathological process, we analysed the retinal gene expression of DBA/2J mice that develop an elevated intraocular pressure by the age of 6 months with subsequent ganglion cell loss. In this study, we identified subunits of the epithelial sodium channel (ENaC) family that are specifically expressed under elevated intraocular pressure. Using reverse transcriptase polymerase chain reaction we observed a significant increase of alpha-ENaC in the neuronal retina of DBA/2J mice when compared with control animals, while beta-ENaC and gamma-ENaC were not detectable in this tissue. Specific immune sera to ENaC subunits showed up-regulation of alpha-ENaC in synaptic and nuclear layers of the retina, and in the retinal pigment epithelium. Consistent with our polymerase chain reaction data, beta-ENaC was not detected by specific antibodies in the retina, while gamma-ENaC was only present in the retinal pigment epithelium under ocular hypertension. Finally, the increase of alpha-ENaC gene expression in the neuronal retina and the retinal pigment epithelium was not observed in other tissues of DBA/2J mice. Since the intraocular pressure is regulated by the transport of aqueous humour across epithelial structures of the eye that in turn is associated with ion flux, the specific up-regulation of ENaC proteins could serve as a protecting mechanism against elevated intraocular pressure.
Dyka
Frank M
FM
Institut für Biochemie, Emil-Fischer-Zentrum, Erlangen, Germany.
May
Christian A
CA
Enz
Ralf
R
D000818:Animals; D001921:Brain / Q000378:metabolism; D053503:Epithelial Sodium Channels; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009798:Ocular Hypertension / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000096:biosynthesis* / Q000235:genetics; D012160:Retina / Q000378:metabolism*; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics
D053503:Epithelial Sodium Channels; D021122:Protein Subunits; D015222:Sodium Channels