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Updated: Dec 27, 2025
An Optic Nerve Crush Injury Murine Model to Study Retinal Ganglion Cell Survival
Published on: April 25, 2011
Correlation between retinal ganglion cell loss and nerve crush force-impulse established with instrumented tweezers
Xiaorong Liu1, Liang Feng1, Ishan Shinde2
1Department of Ophthalmology, Northwestern University, Chicago, IL, USA.
Abstract:
Objectives: Rodent models of optic nerve crush (ONC) have often been used to study degeneration and regeneration of retinal ganglion cells (RGCs) and their axons as well as the underlying molecular mechanisms. However, ONC results from different laboratories exhibit a range of RGC injury with varying degree of axonal damage. We developed instrumented tweezers to measure optic nerve (ON) crush forces in real time and studied the correlation between RGC axon loss and force-impulse, the product of force and duration, applied through the instrumented tweezers in mice.Methods: A pair of standard self-closing #N7 tweezers were instrumented with miniature foil strain gauges at optimal locations on both tweezers' arms. The instrumented tweezers were capable of recording the tip closure forces in the form of voltages, which were calibrated through load cells to corresponding tip closure forces over the operating range. Using the instrumented tweezers, the ONs of multiple mice were crushed with varied forces and durations and the axons in the immunostained sections of the crushed ONs were counted.Results: We found that the surviving axon density correlated with crush force, with longer duration and stronger crush forces producing consistently more axon damage.Discussion: The instrumented tweezers enable a simple technique for measurement of ONC forces in real-time for the first time. Using the instrumented tweezers, experimenters can quantify crush forces during ONC to produce consistent and predictable post-crush cell death. This should permit future studies a way to produce nerve damage more consistently than is available now.
Insights
Researchers developed instrumented tweezers to precisely measure optic nerve crush (ONC) forces in real-time. This innovation allows for consistent and predictable retinal ganglion cell (RGC) axon loss in rodent models.
Area of Science:
- Neuroscience
- Ophthalmology
- Biomedical Engineering
Background:
- Rodent models are crucial for studying retinal ganglion cell (RGC) degeneration and axon regeneration after optic nerve crush (ONC).
- Existing ONC methods lack standardized force application, leading to variable RGC injury and inconsistent experimental outcomes across laboratories.
Purpose of the Study:
- To develop and validate instrumented tweezers for real-time measurement of optic nerve (ON) crush forces in mice.
- To investigate the correlation between applied crush force-impulse and the resulting RGC axon loss.
Main Methods:
- Standard tweezers were instrumented with foil strain gauges to measure tip closure forces in real-time.
- Forces were calibrated using load cells.
- Optic nerves of mice were crushed using the instrumented tweezers with varied forces and durations, followed by axon counting in immunostained sections.
Main Results:
- A direct correlation was observed between surviving axon density and the applied crush force.
- Longer crush durations and stronger crush forces resulted in significantly greater axon damage.
Conclusions:
- Instrumented tweezers provide a simple, real-time method for quantifying ONC forces.
- This technique enables consistent and predictable induction of nerve damage in ONC models.
- Standardized force measurement will improve the reproducibility of future studies on RGC degeneration and regeneration.
