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Updated: Jun 11, 2025
A Mouse Model of Retinal Ischemia-Reperfusion Injury Through Elevation of Intraocular Pressure
Published on: July 14, 2016
Transcriptional responses in a mouse model of silicone wire embolization induced acute retinal artery ischemia and
Yuedan Wang1, Ying Li1, Jiaqing Feng1
1Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China.
Abstract:
Acute retinal ischemia and ischemia-reperfusion injury are the primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model for simulating the retinal ischemic process has hindered progress in developing neuroprotective agents for RAO. We developed a unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model using silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine the duration of ischemia. Immunofluorescence staining, optical coherence tomography, and haematoxylin and eosin staining were utilized to assess changes in major neural cell classes and retinal structure degeneration at two reperfusion durations. Transcriptomics was employed to investigate alterations in the pathological process of UPOAO following ischemia and reperfusion, highlighting transcriptomic differences between UPOAO and other retinal ischemia-reperfusion models. The UPOAO model successfully replicated the acute interruption of retinal blood supply observed in RAO. 60 min of Ischemia led to significant loss of major retinal neural cells and visual function impairment. Notable thinning of the inner retinal layer, especially the ganglion cell layer, was evident post-UPOAO. Temporal transcriptome analysis revealed various pathophysiological processes related to immune cell migration, oxidative stress, and immune inflammation during the non-reperfusion and reperfusion periods. A pronounced increase in microglia within the retina and peripheral leukocytes accessing the retina was observed during reperfusion periods. Comparison of differentially expressed genes (DEGs) between the UPOAO and high intraocular pressure models revealed specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.
Insights
A novel mouse model for retinal artery occlusion (RAO) was developed, simulating acute retinal ischemia and aiding neuroprotection research. This model shows significant neural cell loss and visual impairment after 60 minutes of ischemia.
Area of Science:
- Ophthalmology
- Neuroscience
- Vascular Biology
Background:
- Acute retinal ischemia and ischemia-reperfusion injury cause neural cell death and vision loss in retinal artery occlusion (RAO).
- Developing effective neuroprotective agents for RAO is hindered by the lack of accurate animal models.
- Existing models do not fully replicate the complex ischemic process in RAO.
Purpose of the Study:
- To develop and validate a novel mouse model for simulating acute retinal ischemia and ischemia-reperfusion injury in RAO.
- To evaluate the duration of ischemia required to induce significant retinal damage and visual function impairment.
- To investigate the molecular and cellular changes associated with this new RAO model.
Main Methods:
- A unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model was created using silicone wire embolization and carotid artery ligation.
- Retinal ganglion cell survival and visual function were assessed.
- Immunofluorescence, optical coherence tomography, and H&E staining were used to evaluate retinal structure and cell changes.
- Transcriptomics was employed to analyze molecular alterations during ischemia and reperfusion.
Main Results:
- The UPOAO model effectively mimicked acute retinal blood supply interruption seen in RAO.
- 60 minutes of ischemia resulted in significant retinal neural cell loss and impaired visual function.
- Inner retinal layers, particularly the ganglion cell layer, showed notable thinning.
- Transcriptomic analysis revealed immune cell migration, oxidative stress, and inflammation during reperfusion, with increased microglia and leukocyte infiltration.
- UPOAO model showed specific enrichment in lipid and steroid metabolism genes compared to high intraocular pressure models.
Conclusions:
- The developed UPOAO mouse model accurately replicates key aspects of RAO.
- This model provides a valuable tool for studying pathogenic mechanisms in RAO.
- It serves as a novel platform for screening potential neuroprotective agents and advancing therapeutic research for RAO.
