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Author Spotlight: Developing Precise and Clinically Relevant Models for Studying Secondary Degeneration in Traumatic Optic Neuropathy
Published on: November 29, 2024
Eye-Directed Overpressure Airwave-Induced Trauma Causes Lasting Damage to the Anterior and Posterior Globe: A Model
Courtney Bricker-Anthony1,2, Jessica Hines-Beard1,2, Tonia S Rex1,2
11 Vanderbilt Eye Institute Vanderbilt University School of Medicine , Nashville, Tennessee.
Purpose:
Characterization of the response of the Balb/c mouse to an eye-directed overpressure airwave, with the hypothesis that this mouse strain and model is useful for testing potential therapeutics for the treatment of traumatic eye injury.
Methods:
The left eyes of adult Balb/c mice were exposed to an eye-directed overpressure airwave. Intraocular pressure (IOP) was measured and eyes were inspected for gross pathology changes. Optical coherence tomography and histology were used to examine the structural integrity of the retina and optic nerve. Immunohistochemistry, in vivo molecular fluorophores, and a multiplex enzyme-linked immunosorbent assay were utilized to identify changes in cell death, neuroinflammation, and oxidative stress.
Results:
This model induced a transient increase in IOP, corneal injuries, infrequent large retinal detachments, retinal pigment epithelium (RPE) vacuolization, glial reactivity, and retinal cell death. Both the corneal damage and RPE vacuolization persisted with time. Optic nerve degeneration occurred as early as 7 days postinjury and persisted out to 60 days. Retinal cell death, increased levels of reactive oxygen species, and neuroinflammation were detected at 7 days postinjury.
Conclusions:
The injury profile of the Balb/c mouse is consistent with commonly observed pathologies in blast-exposed patients. The damage is throughout the eye and persistent, making this mouse model useful for testing cell-based therapies.
Insights
This study shows Balb/c mice exposed to airwaves develop eye injuries similar to blast-exposed patients. This validated mouse model is suitable for testing new traumatic eye injury therapeutics.
Area of Science:
- Ophthalmology
- Trauma Research
- Animal Models
Background:
- Traumatic eye injuries, particularly from blast overpressure, pose significant challenges in treatment.
- Developing effective therapeutic strategies requires robust preclinical models that accurately mimic human injury.
Purpose of the Study:
- To characterize the ocular response of Balb/c mice to an eye-directed overpressure airwave.
- To evaluate the utility of this mouse model for testing potential therapeutics for traumatic eye injury.
Main Methods:
- Adult Balb/c mice underwent exposure to an eye-directed overpressure airwave.
- Intraocular pressure, gross pathology, retinal and optic nerve integrity (OCT, histology), cell death, neuroinflammation, and oxidative stress were assessed.
Main Results:
- The model induced transient intraocular pressure increase, corneal injuries, retinal detachments, retinal pigment epithelium (RPE) vacuolization, glial reactivity, and retinal cell death.
- Optic nerve degeneration was observed from 7 to 60 days post-injury.
- Persistent corneal damage, RPE vacuolization, retinal cell death, elevated reactive oxygen species, and neuroinflammation were detected.
Conclusions:
- The Balb/c mouse model exhibits an injury profile consistent with blast-exposed patients.
- The persistent, widespread ocular damage makes this model valuable for evaluating cell-based therapies for traumatic eye injuries.
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