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