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

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 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)

Corneal Thickness

(mm)

Anterior Chamber

Depth (mm)

Lens Thickness

(mm)

Vitreous Chamber

Depth (mm) Reference

HUMAN 23.92 0.55 3.05 4.0 16.32A Photon Accurate Model of the Human 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 An Optical Method, LAPUERTA, and SCHEIN, Vision Research, 1995

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

DOG 20.8 .64 4.29 7.85 10.02

Naturally Occurring Vitreous Chamber—Based Myopia in the Labrador Retriever, Mutti, Zadnik, and Murphy, Investigative Ophthalmology & Visual Science, 1999

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

RAT 5.98 0.25 0.87 3.87 1.51A Revision of the Rat Schematic Eye, MASSOF and CHANG, Vision Research, 1972

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

TonometryCanine

Rabbit

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 FeaturesDog, Rabbit, Rat & Mouse, Primate

Rabbits are able to resist blinking forlong intervals because they have a verystable tear film. This is likely due to the contribution of a lipid contributionfrom the prominent Hardarian gland.Absent in the primate and dog.

Lacrimal & Hardarian Glands

Ocular Anatomic FeaturesDog, Rabbit, Rat & Mouse, Primate

Rabbit Mouse

CanineEyelid

Ocular Anatomic FeaturesDog, Rabbit, Rat & Mouse, Primate

Human Macaque

Primate eyelid

Tarsal plate

Ocular Anatomic FeaturesDog, Rabbit, Rat & Mouse, Primate

Overall Globe Shape :PrimateFovea

Ocular Anatomic FeaturesDog, Rabbit, Rat & Mouse, Primate

Overall Globe Shape :Canine

Ocular Anatomic FeaturesDog, Rabbit, Rat & Mouse, Primate

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 CannalScleral Spur

Ocular Anatomic FeaturesFiltration 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

RetinaFundus

Canine

Rabbit: Merangiotic

Primate

Rat

Retina: Primate Macula

Fovea

Primate Cone Arrestin

Canine Cone ArrestinmERG

The Primate Retina The Cone Mosaic

Mike Nork

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 Retina

Canine Area Centralis Rabbit Medullary Ray

Rat Superior Retina and Phototoxic Degeneration

Optic Nerve Lamina Cribrosa

Primate Dog

Rat: No Lamina Cribrosa