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Updated: May 10, 2026
Induction of Retinal Ischemia-Reperfusion Injury in a Mouse Eye Model
Published on: December 20, 2024
Progressive morphological changes and impaired retinal function associated with temporal regulation of gene
Byung-Jin Kim1, Terry A Braun, Robert J Wordinger
1The North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Abstract:
Retinal ischemia/reperfusion (I/R) injury is an important cause of visual impairment. However, questions remain on the overall I/R mechanisms responsible for progressive damage to the retina. In this study, we used a mouse model of I/R and characterized the pathogenesis by analyzing temporal changes of retinal morphology and function associated with changes in retinal gene expression. Transient ischemia was induced in one eye of C57BL/6 mice by raising intraocular pressure to 120 mmHg for 60 min followed by retinal reperfusion by restoring normal pressure. At various time points post I/R, retinal changes were monitored by histological assessment with H&E staining and by SD-OCT scanning. Retinal function was also measured by scotopic ERG. Temporal changes in retinal gene expression were analyzed using cDNA microarrays and real-time RT-PCR. In addition, retinal ganglion cells and gliosis were observed by immunohistochemistry. H&E staining and SD-OCT scanning showed an initial increase followed by a significant reduction of retinal thickness in I/R eyes accompanied with cell loss compared to contralateral control eyes. The greatest reduction in thickness was in the inner plexiform layer (IPL) and inner nuclear layer (INL). Retinal detachment was observed at days 3 and 7 post- I/R injury. Scotopic ERG a- and b-wave amplitudes and implicit times were significantly impaired in I/R eyes compared to contralateral control eyes. Microarray data showed temporal changes in gene expression involving various gene clusters such as molecular chaperones and inflammation. Furthermore, immunohistochemical staining confirmed Müller cell gliosis in the damaged retinas. The time-dependent changes in retinal morphology were significantly associated with functional impairment and altered retinal gene expression. We demonstrated that I/R-mediated morphological changes the retina closely associated with functional impairment as well as temporal changes in retinal gene expression. Our findings will provide further understanding of molecular pathogenesis associated with ischemic injury to the retina.
Insights
Retinal ischemia/reperfusion (I/R) injury causes progressive vision loss. This study links I/R-induced retinal damage to functional impairment and altered gene expression in mice.
Area of Science:
- Ophthalmology
- Neuroscience
- Molecular Biology
Background:
- Retinal ischemia/reperfusion (I/R) injury is a significant cause of visual impairment.
- The precise mechanisms driving progressive retinal damage after I/R remain incompletely understood.
Purpose of the Study:
- To characterize the pathogenesis of retinal I/R injury by analyzing temporal changes in retinal morphology, function, and gene expression.
- To investigate the molecular mechanisms underlying I/R-induced retinal damage.
Main Methods:
- A mouse model of transient retinal ischemia/reperfusion (I/R) was established.
- Retinal morphology was assessed using H&E staining and SD-OCT.
- Retinal function was evaluated by scotopic ERG.
- Gene expression changes were analyzed using cDNA microarrays and real-time RT-PCR.
- Immunohistochemistry was used to detect retinal ganglion cells and gliosis.
Main Results:
- I/R injury led to a significant reduction in retinal thickness, particularly in the IPL and INL, accompanied by cell loss and retinal detachment.
- ERG measurements showed significant impairment in a- and b-wave amplitudes and implicit times in I/R eyes.
- Microarray analysis revealed temporal changes in gene expression, including clusters related to molecular chaperones and inflammation.
- Immunohistochemistry confirmed Müller cell gliosis in damaged retinas.
Conclusions:
- I/R-mediated morphological changes in the retina are closely associated with functional impairment.
- Temporal alterations in retinal gene expression play a crucial role in the pathogenesis of I/R injury.
- These findings enhance understanding of the molecular mechanisms underlying ischemic retinal injury.
