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Updated: Nov 17, 2025
A Mouse Model of Retinal Ischemia-Reperfusion Injury Through Elevation of Intraocular Pressure
Published on: July 14, 2016
Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor
Anna Y M Wang1, Vickie H Y Wong2, Pei Ying Lee2
1Department of Anatomy & Neuroscience, University of Melbourne, Melbourne, 3010, Australia.
Abstract:
There is increasing evidence for the vulnerability of specific retinal ganglion cell (RGC) types in those with glaucoma and in animal models. In addition, the P2X7-receptor (P2X7-R) has been suggested to contribute to RGC death following stimulation and elevated IOP, though its role in RGC dysfunction prior to death has not been examined. Therefore, we examined the effect of an acute, non-ischemic intraocular pressure (IOP) insult (50 mmHg for 30 min) on RGC function in wildtype mice and P2X7-R knockout (P2X7-KO) mice. We examined retinal function using electroretinogram recordings and individual RGC responses using multielectrode arrays, 3 days following acute IOP elevation. Immunohistochemistry was used to examine RGC cell death and P2X7-R expression in several RGC types. Acute intraocular pressure elevation produced pronounced dysfunction in RGCs; whilst other retinal neuronal responses showed lesser changes. Dysfunction at 3 days post-injury was not associated with RGC loss or changes in receptive field size. However, in wildtype animals, OFF-RGCs showed reduced spontaneous and light-elicited activity. In the P2X7-KO, both ON- and OFF-RGC light-elicited responses were reduced. Expression of P2X7-R in wildtype ON-RGC dendrites was higher than in other RGC types. In conclusion, OFF-RGCs were vulnerable to acute IOP elevation and their dysfunction was not rescued by genetic ablation of P2X7-R. Indeed, knockout of P2X7-R also caused ON-RGC dysfunction. These findings aid our understanding of how pressure affects RGC function and suggest treatments targeting the P2X7-R need to be carefully considered.
Insights
Glaucoma research reveals that elevated intraocular pressure (IOP) impairs retinal ganglion cell (RGC) function, particularly OFF-RGCs. Blocking the P2X7-receptor (P2X7-R) did not prevent this dysfunction and unexpectedly impaired ON-RGCs.
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- Glaucoma is characterized by progressive retinal ganglion cell (RGC) vulnerability.
- The P2X7-receptor (P2X7-R) is implicated in RGC death, but its role in RGC dysfunction is unclear.
- Elevated intraocular pressure (IOP) is a primary risk factor for glaucoma.
Purpose of the Study:
- To investigate the impact of acute IOP elevation on RGC function in wildtype and P2X7-R knockout (P2X7-KO) mice.
- To determine if P2X7-R influences RGC dysfunction following IOP insult.
Main Methods:
- Acute IOP elevation (50 mmHg for 30 min) in wildtype and P2X7-KO mice.
- Retinal function assessed via electroretinogram (ERG) and RGC activity using multielectrode arrays (MEAs) 3 days post-insult.
- Immunohistochemistry to evaluate RGC death and P2X7-R expression.
Main Results:
- Acute IOP elevation caused significant RGC dysfunction without inducing cell death or altering receptive field size.
- OFF-RGCs in wildtype mice exhibited reduced spontaneous and light-evoked activity.
- P2X7-KO mice showed impaired light-evoked responses in both ON- and OFF-RGCs; P2X7-R expression was highest in ON-RGC dendrites.
Conclusions:
- OFF-RGCs are vulnerable to acute IOP elevation, and P2X7-R genetic ablation does not rescue this dysfunction.
- P2X7-R knockout exacerbates RGC dysfunction, affecting both ON- and OFF-RGCs.
- Targeting P2X7-R for glaucoma treatment requires careful consideration due to its complex role in RGC function.
