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Spontaneous ophthalmic lesions in young Swiss mice
M F Hubert1, G Gerin, G Durand-Cavagna
1Merck Sharp & Dohme-Chibret Laboratories, Research Center, France.
Background And Purpose:
Outbred mice are frequently used in toxicity evaluation. Due to their small size, ophthalmologic examination of such animals is difficult with regard to restraint and use of instruments designed for human medicine. The clinical appearance and incidence of spontaneous ophthalmic lesions should be helpful in selecting mice for toxicity studies and allow distinction between intercurrent spontaneous ocular changes and those attributable to drugs or chemicals.
Methods:
Pretest ophthalmologic examinations of about 3,000 4- to 5-week-old Swiss mice, Crl:CD1 (ICR)BR, conducted in 1995 and 1996, provided information about spontaneous ocular changes and their incidence. Eye evaluations were performed after pupil dilatation (0.5% tropicamide instillation), using indirect ophthalmoscopy, and when indicated, a portable slit lamp.
Results:
Lenticular opacities and heterogeneity/prominence were the most common findings (up to 19%) in the anterior segment. Abnormalities of the cornea and iris were detected in up to 4% of mice. Hyaloid artery remnant, as well as isolated cases of floating bodies or hemorrhage, was observed in the vitreous of 12 to 17% of mice. Approximately 2 to 4% of mice had colobomatous fundus, retinal fold, or retinal atrophy. A few mice had chorioretinal atrophy, hemorrhage, or abnormal pattern of the retinal vasculature. Remaining findings consisted of incomplete palpebral fissure, microphthalmia, exophthalmia, ophthalmic hemorrhage, and scleral mass.
Conclusions:
Due to severity of the condition or interference with ocular examination, affected mice should be eliminated from experimental studies. Hence, pretest ocular examinations of mice are indicated in safety-assessment toxicity studies.
Insights
Pretest ocular examinations in mice are crucial for toxicity studies. Identifying spontaneous eye lesions ensures accurate drug safety assessment and experimental validity.
Area of Science:
- Veterinary Ophthalmology
- Toxicology Research
- Preclinical Safety Assessment
Background:
- Outbred mice are standard models for toxicity evaluation.
- Ophthalmologic examination in mice presents challenges due to animal size and instrument limitations.
- Understanding spontaneous ocular lesions is vital for accurate toxicity study interpretation.
Purpose of the Study:
- To document spontaneous ocular changes and their incidence in Swiss mice (Crl:CD1 (ICR)BR).
- To establish baseline ocular health data for selecting appropriate animals in toxicity studies.
- To differentiate drug-induced ocular effects from naturally occurring lesions.
Main Methods:
- Pretest ophthalmologic examinations of approximately 3,000 mice aged 4-5 weeks.
- Pupil dilation using 0.5% tropicamide followed by indirect ophthalmoscopy.
- Portable slit lamp examination was utilized when necessary.
Main Results:
- The most frequent anterior segment findings included lenticular opacities and heterogeneity (up to 19%).
- Vitreous abnormalities, such as hyaloid artery remnant, were observed in 12-17% of mice.
- Retinal and fundic abnormalities (e.g., coloboma, atrophy) occurred in 2-4% of the examined mice.
Conclusions:
- Mice with significant spontaneous ocular lesions or those hindering examination should be excluded from toxicity studies.
- Pretest ocular screening is essential for safety assessment toxicity studies.
- This practice enhances the reliability of toxicity data and animal welfare.