Presence of calpain-induced proteolysis in retinal degeneration and dysfunction in a rat model of acute ocular hypertension

Takayuki Oka, Yoshiyuki Tamada, Emi Nakajima, Thomas R. Shearer, Mitsuyoshi Azuma

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

The purpose of this study was to determine if calpain-induced proteolysis was associated with retinal degeneration or dysfunction in the rat acute ocular hypertensive model. Acute glaucoma was produced by elevation of IOP to 120 mm Hg for 1 hr. Retinal degeneration was evaluated by H&E staining and apoptosis was determined by TUNEL staining in histologic sections of retina. Electroretinogram (ERG) was carried out to evaluate changes in functionality. Activation of calpains was determined by casein zymography and immunoblotting. Total calcium in retina was measured by atomic absorption spectrophotometry. Proteolysis of α-spectrin, tau, cdk5, and p35 (a regulator of cdk5) were evaluated by immunoblotting. The thickness of inner plexiform layer (IPL) and inner nuclear layer (INL), and the number of cells in the ganglion cell layer (GCL) decreased after ocular hypertension. Numerous cells in the INL stained positive for TUNEL and some cells in the outer nuclear layer (ONL) showed TUNEL staining. The a-wave in ERG was temporarily decreased after ocular hypertension and then recovered to normal. In contrast, the b-wave was completely lost. Calpains were activated after ocular hypertension. Activation of calpains was associated with increased calcium in retina. Calpain-dependent proteolysis of α-spectrin, tau, and p35 were observed in retina after ocular hypertension. The results suggested that increased calcium and subsequent proteolysis by activated calpains was associated with the death of inner retinal cells due to acute ocular hypertension in the rat model. Calpain inhibitors may be candidate drugs for treatment of retinal degeneration and dysfunction resulting from glaucoma.

Original languageEnglish (US)
Pages (from-to)1342-1351
Number of pages10
JournalJournal of Neuroscience Research
Volume83
Issue number7
DOIs
StatePublished - May 15 2006

Keywords

  • Calcium
  • Calpain
  • Cdk5/ p25
  • Glaucoma
  • Tau
  • α-spectrin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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