Increased intraocular pressure alters the cellular distribution of HuR protein in retinal ganglion cells - A possible sign of endogenous neuroprotection failure

Biochim Biophys Acta Mol Basis Dis. 2018 Jan;1864(1):296-306. doi: 10.1016/j.bbadis.2017.10.030. Epub 2017 Oct 28.

Abstract

The RNA-binding protein, HuR, modulates mRNA processing and gene expression of several stress response proteins i.e. Hsp70 and p53 that have been postulated to be involved in the pathogenesis of glaucoma, a chronic optic neuropathy leading to irreversible blindness. We evaluated HuR protein expression in retinas and optic nerves of glaucomatous rats and human primary open angle glaucoma patients and its possible impact on stress response mechanisms. We found that the cytoplasmic content of HuR was reduced more extensively in glaucomatous retinas than in optic nerves and this was linked with a declined cytoplasmic Hsp70 level and p53 nuclear translocation. In the optic nerve, the p53 content was decreased as a feature of reactive gliosis. Based on our findings, we conclude that the alteration in the HuR content, observed both in rat glaucoma model and human glaucoma samples, affects post-transcriptionally the expression of genes crucial for maintaining cell homeostasis; therefore, we postulate that HuR may be involved in the pathogenesis of glaucoma.

Keywords: Glaucoma model; Intraocular pressure; Primary open angle glaucoma; RNA-binding proteins; Retinal ganglion cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Case-Control Studies
  • Disease Models, Animal
  • ELAV-Like Protein 1 / genetics
  • ELAV-Like Protein 1 / metabolism*
  • Glaucoma, Open-Angle / genetics
  • Glaucoma, Open-Angle / metabolism
  • Glaucoma, Open-Angle / pathology
  • Humans
  • Intraocular Pressure / genetics
  • Male
  • Neuroprotection / genetics
  • Ocular Hypertension / genetics
  • Ocular Hypertension / metabolism*
  • Ocular Hypertension / pathology
  • Optic Nerve / metabolism
  • Optic Nerve / pathology
  • Rats
  • Rats, Wistar
  • Retinal Ganglion Cells / metabolism*
  • Retinal Ganglion Cells / pathology
  • Tissue Distribution

Substances

  • ELAV-Like Protein 1