Transcriptional responses in a mouse model of silicone wire embolization induced acute retinal artery ischemia and reperfusion

Abstract

Acute retinal ischemia and ischemia-reperfusion injury are primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model simulating the retinal ischemic process has hampered progress in developing neuroprotective agents for RAO. A unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model was developed by employing silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine ischemia duration. Immunofluorescence staining, optical coherence tomography, and hematoxylin and eosin staining were utilized to assess changes in major classes of neural cells 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 seen in RAO. 60-minute ischemia was confirmed to lead the major retinal neural cells loss and visual function impairment. Notable thinning of the inner layer of the retina, 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 non-reperfusion and reperfusion periods. The resident microglia within the retina and peripheral leukocytes which access to the retina were pronounced increased on reperfusion periods. Comparison of differentially expressed genes between the UPOAO and high intraocular pressure models identified specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for the screening of pathogenic genes, promoting further therapeutic research in RAO.