1578 Scientific Reports JAVMA, Vol 242, No. 11, June 1, 2013 AQUATIC ANIMALS T ricaine methanesulfonate is an immersion anesthetic approved in the United States for use in fish; it is commonly used to anesthetize fish for procedures such as manually assisted spawning, weighing, measuring, surgery, transportation, and research. 1 The anesthetic effects of this drug are thought to result from sodium channel blockade in neural tissue. 2 Tricaine methanesul- fonate is a preferred anesthetic for use in fish because it is soluble in water and can be administered by immer- sion and because concentrations are easily adjustable. Additionally, it produces rapid anesthetic induction and recovery (< 5 minutes each). 1,3 Tricaine methanesulfo- nate is absorbed and primarily cleared across the gill epi- thelium, although there is also biotransformation in the liver and potential renal excretion. 4 Although commonly used, MS-222 is reported to have retinotoxic effects in fish, frogs, and humans. 2,5–8 A commonly cited clinical report 7 describes a 62-year-old ichthyologist who developed vision loss with decreased ERG wave amplitudes after chronic low-level exposure to MS-222 over approximately 30 years. The authors of that report 7 based the diagnosis of retinopathy associ- Evaluation of the effects of tricaine methanesulfonate on retinal structure and function in koi carp (Cyprinus carpio) Kate M. Bailey, DVM; Julie E. Hempstead, DVM; Jeremy R. Tobias, DVM; Luke B. Borst, DVM, PhD, DACVP; Alison B. Clode, DVM, DACVO; Lysa P. Posner, DVM, DACVA Objective—To determine whether repeated exposure to clinically relevant concentrations of tricaine methanesulfonate (MS-222) would alter retinal function or induce histologically detectable retinal lesions in koi carp (Cyprinus carpio). Design—Prospective, controlled, experimental study. Animals—18 healthy koi carp. Procedures—2 fish were euthanized at the start of the study, and eyes were submitted for histologic evaluation as untreated controls. Anesthesia was induced in the remaining fish with 200 mg of MS-222/L and maintained with concentrations of 125 to 150 mg/L for a total exposure time of 20 minutes daily on 1 to 13 consecutive days. On days 1, 7, and 13, electro- retinography of both eyes was performed in all fish remaining in the study, and 2 fish were euthanized immediately after each procedure for histologic evaluation of the eyes. Median b- wave amplitudes were compared among study days for right eyes and for left eyes via 1-way repeated-measures ANOVA with a Bonferroni correction for multiple comparisons. Results—Median b-wave amplitudes on days 1, 7, and 13 were 17.7, 20.9, and 17.6 μV, re- spectively, for right eyes and 15.1, 16.9, and 14.3 μV, respectively, for left eyes. No significant differences in b-wave amplitudes were detected among study days. No histopathologic ab- normalities were identified in the retinas of any fish treated with MS-222 or in control fish. Conclusions and Clinical Relevance—Short-term exposure of koi carp to clinically relevant concentrations of MS-222 daily for up to 13 days was not associated with changes in retinal structure or function as measured in this study. (J Am Vet Med Assoc 2013;242:1578–1582) ated with chronic exposure to MS-222 partially on in- formation found in a series of studies 2,5,8 that indicated the in vitro exposure of eye cups (ie, all tissues remain- ing after removal of the cornea, lens, and vitreous from the enucleated eye) to high concentrations of MS-222 resulted in altered ERG waves in retinas of eyes isolated from frogs. Interestingly, 7 months after cessation of ex- posure to MS-222, the vision of the patient described in that report 7 had clinical improvement and his ERG waves had doubled in amplitude. Electroretinography is considered the gold stan- dard to assess retinal function, and b-wave amplitudes provide evidence of the function of inner retinal com- ponents. 9 Results of ERG are useful in differentiating retinal from postretinal blindness because a positive ERG wave is indicative only of retinal function, pro- viding no information regarding the remainder of the visual pathway (eg, optic nerve or visual cortex). Considering that fish are routinely anesthetized with MS-222, it is logical to question whether repeat- ed or prolonged exposure to the drug results in vision loss or retinal damage in these species. In our experi- ence, fish anesthetized repeatedly with MS-222 do not have apparent behavioral changes associated with vi- From the Departments of Molecular and Biomedical Sciences (Bailey, Posner), Clinical Sciences (Hempstead, Clode), and Public Health and Pathobiology (Tobias, Borst), College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607. The authors thank Shane Christian and Sathya Chinnadurai for med- ical consultation and technical assistance. Address correspondence to Dr. Bailey (kate_bailey@ncsu.edu). ABBREVIATIONS ERG Electroretinography MS-222 Tricaine methanesulfonate