Complex neurodegeneration in retina following moderate ischemia induced by bilateral common carotid artery occlusion in Wistar rats

Hideo Yamamoto, Rainald Schmidt-Kastner, Duco I. Hamasaki, Hiroko Yamamoto, Jean-Marie A Parel

Research output: Contribution to journalArticle

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Abstract

Bilateral common carotid artery occlusion (BCCAO) produces moderate levels of ischemia in the retina of rats, which may simulate the inflow disturbances in severe carotid artery disease. ERG changes following acute BCCAO have been well described, but the effects of chronic BCCAO on the histopathology of the retina remain to be characterized in a reproducible model. Chronic BCCAO was induced in halothane-anaesthetized male Wistar rats and the retina fixed after 3, 6, or 24 hr, 1 week, and 2, 4, or 6 months. Cell counts and measurements of retinal layers were performed in H&E stained paraffin sections. Immunohistochemistry with a panel of fourteen antibodies served to examine the survival of different retinal cell class, astrocytic reactions and the expression of acute stress response proteins. A lectin method was used to label activated microglial cells. Microglial activation, heme oxygenase-1 upregulation and caspase-3 cleavage occurred during the first 24 hr in the absence of overt cell death of retinal ganglion cells (RGC). Three waves of neurodegeneration followed. RGCs were affected after 1 week, followed by neurons in the inner nuclear layer at 2 months, and finally photoreceptors at 4 months. Immunomarkers indicated acute damage to horizontal cells and prolonged survival of amacrine cells. In conclusion, chronic BCCAO produced delayed neuronal death in the retina of adult male Wistar rats. The window of moderate changes of at least 1 day may facilitate molecular studies on retinal ganglion cell loss.

Original languageEnglish
Pages (from-to)767-779
Number of pages13
JournalExperimental Eye Research
Volume82
Issue number5
DOIs
StatePublished - May 1 2006

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Common Carotid Artery
Retina
Wistar Rats
Ischemia
Retinal Ganglion Cells
Amacrine Cells
Heme Oxygenase-1
Carotid Artery Diseases
Halothane
Heat-Shock Proteins
Lectins
Caspase 3
Paraffin
Cell Survival
Cell Death
Up-Regulation
Cell Count
Immunohistochemistry
Neurons
Antibodies

Keywords

  • Carotid artery
  • Immunohistochemistry
  • Ischemia
  • Neurodegeneration
  • Photoreceptors
  • Retina
  • Retinal ganglion cells

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Complex neurodegeneration in retina following moderate ischemia induced by bilateral common carotid artery occlusion in Wistar rats. / Yamamoto, Hideo; Schmidt-Kastner, Rainald; Hamasaki, Duco I.; Yamamoto, Hiroko; Parel, Jean-Marie A.

In: Experimental Eye Research, Vol. 82, No. 5, 01.05.2006, p. 767-779.

Research output: Contribution to journalArticle

Yamamoto, Hideo ; Schmidt-Kastner, Rainald ; Hamasaki, Duco I. ; Yamamoto, Hiroko ; Parel, Jean-Marie A. / Complex neurodegeneration in retina following moderate ischemia induced by bilateral common carotid artery occlusion in Wistar rats. In: Experimental Eye Research. 2006 ; Vol. 82, No. 5. pp. 767-779.
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