Biomedical Engineering Reference
In-Depth Information
example, topical application of the alpha-2 agonist apraclonidine
usually causes cats to vomit [
85
], presumably due to systemic
interaction with the chemoreceptor trigger zone in the brain,
whereas this is not a common finding in dogs or humans.
Dogs (Canis lupus familiaris)
. This readily available, well studied
species is generally easily trained and much less aggressive towards
humans than all other laboratory species with the possible exception
rabbits. Laboratory beagles of the Marshall strain are particularly
passive and amenable to handling. Dogs have a relatively large eye
(compared to rodents), allow tonometry without general anesthesia
or sedation, and respond to most anti-glaucoma drug classes includ-
ing adrenergics, cholinergics, beta-blockers, carbonic anhydrase inhi-
bitors, prostaglandins, and cannabinoids [
65
,
67
,
68
,
71
,
86
-
90
].
However, they have a larger cornea and anterior chamber than
humans, greater housing requirements than rabbits, a need for con-
tinual acclimation/socialization to maintain acclimation to tonome-
try, and a diurnal curve in which IOP tends to decline over the course
of the day. Without adequate controls the latter may bemistaken for a
drug effect. Like cats, the mechanism of action of anti-glaucoma
drugs does not always mimic humans, especially in regards to effects
of anti-glaucoma drugs on the pupil. For example, apraclonidine
dilates the canine pupil and latanoprost constricts it, whereas neither
drug consistently alters pupil size in humans [
66
,
67
,
89
].
Rabbit (Oryctolagus cuniculus)
. This relatively docile species has a
large eye and an extensive supporting literature base. Tonometry
does not require sedation or anesthesia and can often be accom-
plished by one individual (versus two for the other species discussed
here with the possible exception of sedated monkeys). However,
they have a number of potentially significant ocular anatomical and
physiological differences from humans including relatively low tear
production, an increased sensitivity to ocular irritation, a much
thinner cornea and sclera which reduces ocular rigidity, a fragile
blood:aqueous barrier that is easily broken down, a large lens, a
markedly different blood supply to the retina and a naturally deeply
cupped optic disc ([
91
,
92
], Table
1
). The presence of albinism in
some strains may also alter the pharmacokinetics and efficacy of
drugs which have significant pigment binding. The thinner cornea
tends to cause tonometers to underestimate true IOP and the low
ocular rigidity makes the eye very susceptible to artifactual increases
in IOP due to compression of the globe by handling, eyelid squeez-
ing, or the animal retracting the globe as it seeks to avoid the probe
tip touching the cornea. These factors, plus a somewhat “fearful”
demeanor which leads to breath holding and causes rapid changes
in systemic blood pressure and heart rate results in IOP that may
naturally vary 3-5 mmHg in 1 min [
31
,
32
]. IOP also may be
elevated after common handling procedures such as after being
