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Updated: Oct 11, 2026
A Mouse Model of Retinal Ischemia-Reperfusion Injury Through Elevation of Intraocular Pressure
Published on: July 14, 2016
Involvement of calpain isoforms in ischemia-reperfusion injury in rat retina
Y R Sakamoto1, T R Nakajima, C R Fukiage
1Research Laboratories, Senju Pharmaceutical Corporation Limited, Kobe, Japan.
Purpose:
Much evidence has accumulated suggesting that activation of calpain causes neuronal cell death in ischemic brain. However, little is known about the involvement of calpain in retinal cell death in ischemic injury. Thus, the purpose of present study was to investigate the involvement of calpain isoforms (m- and mu-calpain) in ischemia-reperfusion injury in retina from rat.
Methods:
Retinal ischemia was produced by occlusion of the central retinal artery for one hour, and this was followed by reperfusion for seven days. Calpain mRNAs, calpain activities, total calcium content and proteolysis of alpha-spectrin were determined in retina. Effect of a calpain inhibitor SJA6017 was histologically tested in retinal injury after ischemia-reperfusion.
Results:
Following retinal ischemia, most of cells in the ganglion cell layer were sloughed off by day 1 after reperfusion, followed by loss of cells in the inner plexiform layer on day 3 and loss of cells in the inner nuclear layer by day 5. These morphologic changes were accompanied by several presumptive biochemical indicators of calpain activation: increased calcium, proteolysis of alpha-spectrin (a sensitive substrate for calpains), decreased caseinolytic activity for both calpains (suggesting calpain activation followed by autolytic degradation), increased mRNA levels for mu-calpain and calpastatin - the endogenous inhibitor of calpains - and decreased mRNA levels for mu-calpain. Moreover, the calpain inhibitor SJA6017 protected the reduction of cell density in the ganglion cell layer after ischemia-reperfusion.
Conclusion:
These results suggest that calpain isoforms may play an important role in neuronal cell death induced by retinal ischemia-reperfusion injury in rat.
Insights
Calpain activation contributes to retinal cell death following ischemia-reperfusion injury. Inhibiting calpain (calcium-activated protease) protected retinal cells, suggesting a therapeutic target for vision loss.
Area of Science:
- Neuroscience
- Ophthalmology
- Biochemistry
Background:
- Calpain activation is linked to neuronal death in brain ischemia.
- The role of calpains in retinal ischemia-reperfusion injury remains largely unknown.
- Investigating calpain isoforms (m- and mu-calpain) in retinal injury is crucial.
Purpose of the Study:
- To investigate the involvement of calpain isoforms (m- and mu-calpain) in rat retinal ischemia-reperfusion injury.
- To assess the impact of calpain activation on retinal cell death and biochemical markers.
- To evaluate the protective effect of a calpain inhibitor on retinal injury.
Main Methods:
- Rat retinal ischemia was induced by central retinal artery occlusion for 1 hour, followed by 7 days of reperfusion.
- Measurements included calpain mRNA levels, calpain activity, calcium content, and alpha-spectrin proteolysis.
- The calpain inhibitor SJA6017 was used to assess histological protection against ischemia-reperfusion injury.
Main Results:
- Retinal ischemia caused significant cell loss in the ganglion cell layer, inner plexiform layer, and inner nuclear layer.
- Biochemical indicators of calpain activation, including increased calcium and alpha-spectrin proteolysis, were observed.
- The calpain inhibitor SJA6017 demonstrated a protective effect on ganglion cell density after ischemia-reperfusion.
Conclusions:
- Calpain isoforms appear to play a significant role in neuronal cell death during retinal ischemia-reperfusion injury.
- These findings suggest calpains as potential therapeutic targets for treating ischemic retinal damage.
- Further research into calpain inhibition could offer new strategies for preventing vision loss.
