Related Experiment Video
Updated: Jun 23, 2026
Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs
Published on: July 23, 2016
Bupivacaine-Induced Regeneration in Rabbit Extraocular Muscles: Implications for the Treatment of Strabismus
Jolene C Rudell1, Ashley Liang1, Vaidehi Bhavaraju1
1Department of Ophthalmology, University of California San Diego, La Jolla, California.
Objective:
Local injections such as bupivacaine are used to treat strabismus, although the mechanism of its clinical effects is unknown. The purpose of this study is to analyze the effects of bupivacaine on extraocular muscle regeneration in a preclinical model.
Design:
Laboratory study.
Controls:
Three-month-old male New Zealand white rabbits with age- and sex-matched saline injection controls and uninjected controls.
Methods:
One superior rectus muscle per animal was injected with either 3% bupivacaine or saline control and harvested at 1 week, 1 month, or 3 months after treatment. Histomorphometric analysis was used to determine the effects of bupivacaine on extraocular muscles. Data were analyzed for the global and orbital layer separately, as well as the entire muscle cross-sectional area.
Main Outcome Measures:
Muscle morphology, markers of muscle regeneration, muscle size.
Results:
Treatment with 3% bupivacaine had a myodestructive effect on the injected extraocular muscle, with disruption of myofiber organization and areas of missing myofibers. However, even 1 week after injection, we observed significantly more embryonic myosin heavy chain-positive myofibers, indicating newly regenerated myofibers, in the bupivacaine group compared with the saline group. Embryonic myosin heavy chain was still significantly expressed at 1 month after bupivacaine injection in extraocular muscles, in stark contrast to skeletal muscles elsewhere in the body where embryonic myosin heavy chain expression decreases 1 to 2 weeks after injury. There was a significant increase in the density of muscle stem cells and myofibers with centralized nuclei 3 months after bupivacaine injection compared with saline in both the orbital and global layers. Muscle size and extracellular matrix components were not increased at 3 months after bupivacaine injection compared with saline.
Conclusions:
Bupivacaine's effects on extraocular muscles may be explained in part by bupivacaine triggering a regenerative response, initially forming new myofibers and increasing the number of muscle stem cells to exert its effects as a treatment for strabismus.
Financial Disclosures:
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
