Ocular Anatomy and Variations in
Laboratory Animals
Rodent, Rabbit, Primate, Dog
Dick Dubielzig
Anatomy is Important
• Is there an adequate body of experience in the
species of choice?
• Is the ocular anatomy appropriate for the
procedures to be done?
• What is the best species to answer the question?
• Are there particular anatomic features that might
impact the experimental design?
• What is unique about the ocular anatomy in the
different species?
• What are the background lesions in each species?
• Albino vs pigmented
Mammalian
Evolution
Schlemm’s Canal
&
Atapetal Fundus
Rat
Holangiotic Retina
Merangiotic Retina
Rabbit
Is there an adequate body of
experience in the species of choice?
• Species often used in toxicolgy studies
where the eye is a target
– Macaque, Rabbit, Rats of Mice, Dogs
• Species often used in basic vision science
research but not toxicology studies
– Cats, Ground Squirrels, Fruitfly, Chicken
• Species being put forward as having
particular advantages in toxicology studies
– Squirrel Monkey, Mini-pig
Is the ocular anatomy appropriate
for the procedures to be done?
• Is the eye size adequate size for procedures?
• Does the surgical or diagnostic instrumentation
work in the species?
• Does the ocular anatomy impact drug delivery or
pharmacokinetics?
Is the ocular anatomy appropriate
for the procedures to be done?
• Is the eye size adequate size for procedures?
– Problems with using rodents because of the small eye size and
the inaccessibility of the vitreous
• Intraocular pressure measurement is not easily done
– Rebound tonometry on trained mice or manometry
• Intravitreous injection or sampling is not easily done
• Diagnostic examination and procedures require experience and training
that may or may not be automatically available even with board certified
specialists
– Ophthalmoscopy
– Electrophysiology
– Fluorescein angiography
Mouse Eye
Ocular Dimentions
Axial
Length
(mm)
HUMAN
MONKEY
CAT
23.92
Corneal
Thickness
(mm)
0.55
Anterior
Chamber
Depth
(mm)
3.05
Lens
Thickness
(mm)
4.0
Vitreous
Chamber
Depth
(mm)
16.32
Reference
A Photon Accurate Model of the
Human Eye, Deering, ACM Transactions
on Graphics, 2005
17.92
0.55
3.24
2.98
11.3
A Four-surface Schematic Eye of
Macaque Money Obtained by An
Optical Method, LAPUERTA, and
SCHEIN, Vision Research, 1995
22.3
0.68
4.52
8.5
8.13
The Schematic Eye In The Cat
Vakkur and Bishop, Vision Research, 1963
Naturally Occurring Vitreous
Chamber—Based Myopia in the
Labrador Retriever, Mutti, Zadnik, and
Murphy, Investigative Ophthalmology &
Visual Science, 1999
DOG
20.8
.64
4.29
7.85
10.02
RABBIT
18.1
0.4
2.9
7.9
6.2
A Schematic Eye for the Rabbit,
HUGHES, Vision Research, 1972
1.51
A Revision of the Rat Schematic
Eye, MASSOF and CHANG, Vision
Research, 1972
RAT
5.98
0.25
0.87
3.87
Is the ocular anatomy appropriate
for the procedures to be done?
• Does the surgical or diagnostic instrumentation
work in the species?
– Tonometry in rodents
– Devises designed for the human eye have to be
retooled to use the rodent model
– Vitrectomy instrument: Macaques vs Human
– Choosing the appropriate site for intravitrel
injection or aspiration
– Glaucoma drainage devise in the rabbit eye
Rabbit
Tonometry
Canine
Is the ocular anatomy appropriate
for the procedures to be done?
• Does the ocular anatomy impact drug delivery or
pharmacokinetics?
– The relative % of ocular surface compared to the volume of the
globe is larger in rodents than large animals.
– The distance between the ocular surface and internal ocular tissues
is shorted in rodents tan large animals.
Canine
Mouse
What is the best species to answer the
question?
• Is a particular model of disease better defined or
more authentic in a particular species?
– Glaucoma models
– Laser models for CNV
– Transgenic mouse models of AMD
• Is a more human-like anatomy and physiology
important?
– There is a monkey bias in the ophthalmic drug delivery
world because of the marked similarity between monkey
and human eyes
•
•
•
•
Fovea
Accommodation
Outflow
Lids, tear film, orbital anatomy
Ocular Anatomic Features
Dog, Rabbit, Rat & Mouse, Primate
Lacrimal & Hardarian Glands
Rabbits are able to resist blinking for
long intervals because they have a very
stable tear film. This is likely due to
the contribution of a lipid contribution
from the prominent Hardarian gland.
Absent in the primate and dog.
Ocular Anatomic Features
Dog, Rabbit, Rat & Mouse, Primate
Mouse
Rabbit
Eyelid
Canine
Ocular Anatomic Features
Dog, Rabbit, Rat & Mouse, Primate
Primate eyelid
Tarsal plate
Human
Macaque
Ocular Anatomic Features
Dog, Rabbit, Rat & Mouse, Primate
Fovea
Overall Globe Shape :Primate
Ocular Anatomic Features
Dog, Rabbit, Rat & Mouse, Primate
Overall Globe Shape :Canine
Ocular Anatomic Features
Dog, Rabbit, Rat & Mouse, Primate
Overall Globe Shape :Rodent
Ocular Anatomic Features
Dog, Rabbit, Rat & Mouse, Primate
Primate Vestigial Nictitans
Hairs
Rabbit Nictitans
Rat Vestigial Nictitans
Nictitans (Third Eyelid)
Canine Nictitans
(Third Eyelid)
Ocular Anatomic Features
Filtration Apparatus Primate
Scleral Spur
Schlemm’s Cannal
Ocular Anatomic Features
Filtration Apparatus Dog
Angular Aqueous
Plexus
Primary Pectinate
Ciliary Cleft
Ocular Anatomic Features
Filtration Apparatus Rat & Rabbit
Schlemm’s Cannal
Rat
Rabbit
Accommodation
Ciliary Muscle
Tapetum Lucidum
Eye Shine Canine
Nontapetal
Tapetal
Tapetal
Retina
Fundus
Canine
Rabbit:
Merangiotic
Primate
Rat
Retina: Primate Macula
Fovea
mERG
Canine Cone
Arrestin
Primate Cone
Arrestin
The Primate Retina
The Cone Mosaic
Mike Nork
Adaptive Optics
Variability in Red/Green Cone Ratio among Individuals
Roorda A and Williams DR, Nature 1999
Cone Opsoins
Green vs Red
Green vs Blue
The Visual Streak and Superior
Retina
Canine Area Centralis
Rabbit Medullary Ray
Rat Superior Retina and Phototoxic Degeneration
Optic Nerve
Primate
Lamina Cribrosa
Rat: No Lamina Cribrosa
Dog