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OCULAR
Preclinical Ocular Considerations
in Laboratory Rabbits
Introduction / Background
Laboratory rabbits are most commonly
used for ocular toxicology, device, and
drug studies due to the availability of
normative data, their large eyes, and
their relatively low cost compared with
other laboratory animals. However,
spontaneous ocular lesions will occur in
these animals, detrimentally affecting study
results and study outcomes. Specifically,
ocular abnormalities that are present but
undetected at the start of a study may be
reported as study-related findings, and
pre-existing histopathologic abnormalities
may be interpreted as resulting from the
device or drug therapy. Previous research
has shown that the incidence of these
lesions may be tracked when interactions
between sex, breed, and supplier are
quantified. Incidence of Spontaneous
Ocular Lesions in Laboratory Rabbits, a
study performed by Dana Holve, Karen
Mundwiler, and Stacy Pritt, retrospectively
evaluated ophthalmic examination records
of rabbits screened between April 2008 and
April 2010. These 1840 records represented
572 black Dutch Belted (DB), 1022 New
Zealand White (NZW), and 246 NZW ×
New Zealand Red F1 crosses (WRF1).
Ocular prescreening can reveal subtle defects.
A total of 177 rabbits (9.6%) and 233 eyes
(6.3%) were affected by ocular lesions.
The most common structure affected was
the cornea in 5.7% of rabbits (DB 11.7%,
NZW 3.0%, and NZR [New Zealand Red]
3.3%). This data suggests that lesions are
more prevalent than once thought and their
affluence must be addressed.
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Ocular prescreening is
a very effective way to
identify ocular defects, and
affected animals can then
be excluded from a study.
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Tel: 610-280-7300
San Diego, CA 92111
Tel: 858-560-9000
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Complete ocular prescreening examinations
include external examination of the lids and
slit-lamp biomicroscopy, with or without
indirect ophthalmoscopy. Common
conditions to rule out include inflammation,
cataracts, and corneal defects. Rabbits
affected by one or more of these conditions
should not be placed in a study involving
ocular assessment. This paper serves to
elucidate the ways in which spontaneous
ocular lesions are formed and the ways in
which researchers may preemptively avoid
rabbits with these confounding lesions.
Problem Statement
A wide array of spontaneous ocular
lens defects in rabbits may occur due to
infectious, environmental, or genetic causes.
Pathologies of the lens may result from a
lens-induced uveitis due to Encephalitozoa
cuniculi, an obligate intracellular parasite.
Cage and facility maintenance can help
decrease the presence of these eukaryotic
organisms. Also, cataracts have been
described as idiopathic findings in older
rabbits and due to incidental or familial
causes (consistent with an autosomal
recessive mode of inheritance) in young
animals. Genetic defects within succeeding
generations of rabbits may be avoided
when affected animals are removed from
the breeding process. Furthermore, various
environmental factors can also contribute
to lens defects. Research has shown that
differences among sources of supplies
such as nesting materials and shipping
Incidence of Rabbits with Affected Ocular Structure
Group
Cornea
Lens
Iris
Vitreous
All Rabbits
5.7%
3.6%
0.2%
0.3%
Dutch Belted
11.7%
2.1%
0.2%
0.2%
New Zealand White
3.0%
4.6%
0.2%
0.3%
New Zealand Red
3.3%
3.3%
0%
0.4%
Supplier A
4.7%
5.2%
0.3%
0.3%
Supplier B
15.1%
1.4%
0.3%
0.3%
Supplier C
0%
0%
0%
0%
Supplier D
3.6%
4.8%
0.1%
0.4%
Supplier E
0.5%
1.1%
0%
0%
containers may lead to different rates of
lesions, especially when sex is also taken
into account. However, the rates of lesions
cannot necessarily be determined for every
supplier/sex/breed combination because
not every sex and breed can be obtained
from a given supplier. Rabbits acquired
from suppliers with a high incidence of
spontaneous lesions among their animals
are costly both in terms of resources—
affected rabbits must be housed but cannot
be placed on an ocular study—and time
—studies are delayed due to inadequate
numbers of rabbits free of ocular lesions.
Thus, it is vitally important that researchers
take into account the breed of rabbit being
used in a study as well as the facility from
which they came.
Proposed Solution
Spontaneous ocular lesions within
laboratory rabbits have proven to have a
perpetual negative effect on ocular research;
however, there are multiple solutions
available for limiting the ways in which
these lesions may disrupt studies. One
way a company or research facility may
alleviate issues arising from having rabbits
with spontaneous ocular lesions is by still
including rabbits with lesions but using
the lesioned eye as the untreated control
in the study. In addition, rabbits excluded
from ocular research protocols can still be
used in non-ocular studies, but not every
facility may have this option. Overall,
a facility should limit the number of
rabbits received with spontaneous ocular
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lesions. This restriction can be achieved
by selecting the breed, sex, and supplier
most appropriate for a given study and by
taking the necessary precautions. Corneal
lesions are common in rabbits because of
their environment, diet, lid abnormalities,
and heritability; but if identified, they can
be easily dealt with. Nesting material and
fighting between rabbits in different cages
largely contributes to the traumatic corneal
lesions that occur prior to arrival (before or
during shipment). This is a trivial problem
that can be resolved if rabbits are singlehoused and selected nesting material has no
history of irritation.
A first step in eliminating ocular lesions
within rabbits starts when the breeders only
ship rabbits that pass ocular prescreening.
In this way, fewer rabbits have to be rejected
after arriving at the testing facility. In
addition, facilities that eliminate rabbits
with ocular lesions from their breeding
program can decrease the incidence of
spontaneous ocular lesions, because many
defects are congenital. Lesions may still
develop during shipment, from trauma or
aging, as previously stated, necessitating a
second examination at the testing facility.
This second examination is pivotal if
a researcher does not want any defect
within the animals before the start of a
study. Regular ocular screenings of rabbit
breeding colonies also allow vendors to
remove affected animals from the breeding
program, given that defects like corneal
dystrophy are heritable.
Conclusion
Investigators should always consider facility,
breed, and sex when choosing rabbits for
use in ophthalmic studies. As previously
shown, data were evaluated to determine
the overall incidence of ocular lesions in
any structure by comparing sex, breed,
and supplier. Of all affected rabbits, the
cornea accounted for 58.8% of lesions,
whereas the lens, vitreous, and iris were
affected at rates of 37.9%, 1.7%, and
2.8%, respectively. Overall, eliminating
affected rabbits from breeding colonies,
performing various prescreening exams,
and examining the breeding facility before
purchasing the laboratory animals are all
ways these lesions may be controlled and
their impact reduced.
Appendix- References
1. Andrew SE. 2002. Corneal diseases in rabbits.
Vet Clin North Am Exot Anim Pract 5:341–356.
2. Fox JG, Shalev M, Beaucage CM, Smith M. 1979.
Congenital entropion in a litter of rabbits. Lab Anim
Sci 29:509–511.
3. Gelatt KN. 1975. Congenital cataract in a litter of
rabbits. J Am Vet Med Assoc 167:598–599.
4. Giordano C, Weigt A, Vercelli A, Rondena M,
Grilli G, Giudice C. 2005. Immunohistochemical
identification of Encephalitozoon cuniculi in
phacoclastic uveitis in four rabbits. Vet Ophthalmol
8:271–275.
8. McDonald TO, Shadduck JA. 1997. Eye irritation,
p 579–582. In: Marzulli FN, Maibach HI, editors.
Modern advances in toxicology, vol 4: dermatoxicology
and pharmacology. Washington (DC): Hemisphere
Publishing Corporation.
9. McMaster PRB. 1960. Decreased aqueous outflow
in rabbits with hereditary buphthalmia. Arch
Ophthalmol 64:388–391.
10. Moore CP, Dubielzig R, Glaza SM. 1987.
Anterior corneal dystrophy of American Dutch belted
rabbits: biomicroscopic and histopathological findings.
Vet Pathol 24:28–33.
11. Munger RJ, Langevin N, Podval J. 2002.
Spontaneous cataracts in laboratory rabbits.
Vet Ophthalmol 5:177–181.
12. Port CD, Dodd DC. 1983. Two cases of corneal
epithelial dystrophy in rabbits. Lab Anim Sci
33:587–588.
13. Rubin LF, Weisse I. 1992. Species differences
relevant for ocular toxicity studies. Species differences
relevant for ocular toxicity studies, p 177–191. In:
Hockwin O, Green K, Rubin LF, editors. Manual of
oculotoxicity testing of drugs. New York (NY): Gustav,
Fisher and Verlag.
14. Sebesteny A, Sheraidah GAK, Trevan DJ,
Alexander RA, Ahmed AI. 1985. Lipid keratopathy
and atheromatosis in an SPF laboratory rabbit colony
attributable to diet. Lab Anim 19:180–188.
15. Spence S. 2003. The Dutch-belted rabbit: an
alternative breed for developmental toxicity testing.
Birth Defects Res B Dev Reprod Toxicol 68:439–488.
16. Tesluk GC, Peiffer RL, Brown D. 1982. A clinical
and pathological study of inherited glaucoma in New
Zealand White rabbits. Lab Anim 16:234–239.
17. Wolfer J, Grahn B, Wilcock B, Percy D. 1993.
Phacoclastic uveitis in the rabbit. Progress in
Veterinary and Comparative Ophthalmology 3:92–97.
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5. Gwin RM, Gelatt KN. 1977. Bilateral ocular
lipidosis in a cottontail rabbit fed an all-milk diet.
J Am Vet Med Assoc 171:887–889.
6. Holve D, Mundwiler K, Pritt S. 2010. Incidence
of spontaneous ocular lesions in laboratory rabbits.
J Am Assoc Lab Anim Sci 49:687.
7. Institute for Laboratory Animal Research. 1996.
Guide for the care and use of laboratory animals.
Washington (DC): National Academies Press.
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Exton, PA 19341
Tel: 610-280-7300
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Tel: 858-560-9000
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absorption.com
© 2013 Absorption Systems
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