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Ocular Anatomy and Variations in

Laboratory AnimalsRodent, Rabbit, Primate, Dog

Dick Dubielzig



Anatomy is Important

• Is there an adequate body of experience in thespecies of choice?

• Is the ocular anatomy appropriate for theprocedures to be done?

• What is the best species to answer the question?

• Are there particular anatomic features that mightimpact the experimental design?

• What is unique about the ocular anatomy in thedifferent species?

• What are the background lesions in each species?

• Albino vs pigmented



MammalianEvolution



Schlemm’s Canal&

Atapetal Fundus



Holangiotic Retina

Merangiotic Retina

Rat

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 scienceresearch but not toxicology studies

– Cats, Ground Squirrels, Fruitfly, Chicken

• Species being put forward as havingparticular 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 orpharmacokinetics?




for the procedures to be done?• Is the eye size adequate size for procedures?

– Problems with using rodents because of the small eye size andthe 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 certifiedspecialists

– Ophthalmoscopy

– Electrophysiology

– Fluorescein angiography

Mouse Eye



Ocular Dimentions

AxialLength(mm)

CornealThickness(mm)

Anterior

ChamberDepth(mm)

LensThickness(mm)

Vitreous

ChamberDepth(mm) Reference

HUMAN 23.92 0.55 3.05 4.0 16.32A Photon Accurate Model of theHuman Eye, Deering, ACM Transactions

on Graphics, 2005

MONKEY 17.92 0.55 3.24 2.98 11.3

A Four-surface Schematic Eye of

Macaque Money Obtained by AnOptical Method, LAPUERTA, and

SCHEIN, Vision Research, 1995

CAT 22.3 0.68 4.52 8.5 8.13The Schematic Eye In The CatVakkur and Bishop, Vision Research, 1963

DOG 20.8 .64 4.29 7.85 10.02

Naturally Occurring VitreousChamber—Based Myopia in the

Labrador Retriever, Mutti, Zadnik, andMurphy, Investigative Ophthalmology &

Visual Science, 1999

RABBIT 18.1 0.4 2.9 7.9 6.2A Schematic Eye for the Rabbit,HUGHES, Vision Research, 1972

RAT 5.98 0.25 0.87 3.87 1.51A Revision of the Rat SchematicEye, MASSOF and CHANG, Vision

Research, 1972




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 beretooled to use the rodent model

– Vitrectomy instrument: Macaques vs Human

– Choosing the appropriate site for intravitrelinjection or aspiration

– Glaucoma drainage devise in the rabbit eye

Tonometry

Canine

Rabbit

I th l t i t




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 theglobe 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

Wh t i th b t i t th



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 physiologyimportant?

– There is a monkey bias in the ophthalmic drug deliveryworld because of the marked similarity between monkeyand human eyes

• Fovea

• Accommodation

• Outflow• Lids, tear film, orbital anatomy

O l A i F



Ocular Anatomic FeaturesDog, Rabbit, Rat & Mouse, Primate

Rabbits are able to resist blinking for

long intervals because they have a verystable tear film. This is likely due to

the contribution of a lipid contribution

from the prominent Hardarian gland.

Absent in the primate and dog.

Lacrimal & Hardarian Glands



Ocular Anatomic Features

Dog, Rabbit, Rat & Mouse, PrimateRabbit Mouse

CanineEyelid




Dog, Rabbit, Rat & Mouse, Primate

Human Macaque

Primate eyelid

Tarsal plate





Overall Globe Shape :Primate

Fovea





Overall Globe Shape :Canine





Overall Globe Shape :Rodent




Ocular Anatomic FeaturesDog, Rabbit, Rat & Mouse, Primate

Primate Vestigial Nictitans

Nictitans (Third Eyelid)

Rabbit Nictitans

Rat Vestigial Nictitans

Hairs



Canine Nictitans

(Third Eyelid)




Ocular Anatomic FeaturesFiltration Apparatus Primate

Schlemm’s Cannal

Scleral Spur

O l A i F




Filtration Apparatus Dog

Primary Pectinate

Ciliary Cleft

Angular Aqueous

Plexus




Ocular Anatomic FeaturesFiltration Apparatus Rat & Rabbit

Rat Rabbit

Schlemm’s Cannal



Accommodation

Ciliary Muscle



Tapetum Lucidum

Nontapetal Tapetal Tapetal

Eye Shine Canine

Retina



Retina

Fundus

Canine

Rabbit:Merangiotic

Primate

Rat



Retina: Primate Macula

F



Fovea

Primate Cone

ArrestinCanine Cone

ArrestinmERG

The Primate Retina



The Primate Retina

The Cone Mosaic Mike Nork

Adaptive Optics



Adaptive Optics

Roorda A and Williams DR, Nature 1999

Variability in Red/Green Cone Ratio among Individuals



Cone Opsoins

Green vs Red Green vs Blue

The Visual Streak and Superior



The Visual Streak and Superior

Retina

Canine Area Centralis Rabbit Medullary Ray

Rat Superior Retina and Phototoxic Degeneration

Optic Nerve



pLamina Cribrosa

PrimateDog

Rat: No Lamina Cribrosa

Am Colt Ox Red an At

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