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Updated: Jul 3, 2026
A Murine Model of Ischemic Retinal Injury Induced by Transient Bilateral Common Carotid Artery Occlusion
Published on: November 12, 2020
Molecular and histological changes following central retinal artery occlusion in a mouse model
Nitza Goldenberg-Cohen1, Shimrit Dadon, Bat-Chen R Avraham
1Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, Israel. ncohen1@gmail.com
Abstract:
The aim of this study was to characterize the molecular and histological changes that occur in the retina following central retinal artery occlusion (CRAO) in a mouse model. CRAO was induced in 60 mice by laser photoactivation of intravenously injected rose bengal. Mice were sacrificed at 3, 6, 12, and 24h and 7 and 21 days after CRAO induction for molecular analysis (5-13 mice/time point) and histological and apoptosis studies (3-4 mice/time point). Fundus examination and fluorescein angiography were also performed at various points. Retinal mRNA was analyzed for expression of T-cell antigen 1 (Thy-1), vascular endothelial growth factor (VEGF), heme oxygenase-1 (HO-1), and hypoxia-induced factor 1 alpha (HIF-1 alpha) using real-time polymerase chain reaction. The results showed that at 6-24h following CRAO induction, the retina was edematous, with interrupted blood perfusion. Fluorescein angiography showed reperfusion at 6h, and TdT-mediated dUTP nick end-labeling (TUNEL) assay revealed an increase in apoptotic cells in the first 24h. On histological sections, nuclear loss in the inner retinal layers was maximal on day 21. Thy-1 expression decreased to 30% of baseline (P
Insights
Central retinal artery occlusion (CRAO) in mice induces retinal apoptosis and cell loss, decreasing T-cell antigen 1 (Thy-1) expression. This mouse model of CRAO shows significant molecular and histological changes relevant to human disease.
Area of Science:
- Ophthalmology
- Molecular Biology
- Pathology
Background:
- Central retinal artery occlusion (CRAO) is a critical condition leading to vision loss.
- Understanding the molecular and histological changes post-CRAO is crucial for developing effective treatments.
- Mouse models offer a valuable platform for studying retinal ischemia and reperfusion injury.
Purpose of the Study:
- To characterize the molecular and histological retinal changes following central retinal artery occlusion (CRAO) in a mouse model.
- To investigate the temporal expression patterns of key genes (Thy-1, VEGF, HO-1, HIF-1 alpha) after CRAO.
- To assess retinal apoptosis and cell loss in response to induced CRAO.
Main Methods:
- Central retinal artery occlusion (CRAO) induced in 60 mice via laser photoactivation of rose bengal.
- Molecular analysis of retinal mRNA using real-time polymerase chain reaction at multiple time points (3h to 21 days).
- Histological examination, apoptosis assessment (TUNEL assay), funduscopy, and fluorescein angiography.
Main Results:
- CRAO induced retinal edema, interrupted perfusion, and reperfusion by 6h.
- Increased apoptotic cells observed within the first 24h, with maximal nuclear loss in inner retinal layers by day 21.
- Significant decrease in T-cell antigen 1 (Thy-1) expression; increased heme oxygenase-1 (HO-1) expression peaking at 12h; transient increase in vascular endothelial growth factor (VEGF).
Conclusions:
- CRAO in mice leads to significant inner retinal apoptosis and cell loss by day 21.
- Downregulation of Thy-1 and upregulation of HO-1 are key molecular events following CRAO.
- The mouse model mimics human CRAO, providing insights for clinical management strategies.
