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

Schlemms 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) Corneal Thickness (mm) Anterior Chamber Depth (mm) Lens Thickness (mm) Vitreous Chamber Depth (mm)

Reference
A Photon Accurate Model of the Human Eye, Deering, ACM Transactions on Graphics, 2005 A Four-surface Schematic Eye of Macaque Money Obtained by An Optical Method, LAPUERTA, and SCHEIN, Vision Research, 1995 The Schematic Eye In The Cat Vakkur and Bishop, Vision Research, 1963 Naturally Occurring Vitreous ChamberBased Myopia in the Labrador Retriever, Mutti, Zadnik, and Murphy, Investigative Ophthalmology & Visual Science, 1999 A Schematic Eye for the Rabbit, HUGHES, Vision Research, 1972 A Revision of the Rat Schematic Eye, MASSOF and CHANG, Vision Research, 1972

HUMAN MONKEY CAT

23.92 17.92 22.3 20.8 18.1 5.98

0.55 0.55 0.68 .64 0.4 0.25

3.05 3.24 4.52 4.29 2.9 0.87

4.0 2.98 8.5 7.85 7.9 3.87

16.32 11.3 8.13 10.02 6.2 1.51

DOG RABBIT RAT

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

Tonometry Canine

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 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
Rabbit Mouse

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 Schlemms Cannal

Ocular Anatomic Features

Filtration Apparatus Dog Angular Aqueous Plexus Primary Pectinate

Ciliary Cleft

Ocular Anatomic Features

Filtration Apparatus Rat & Rabbit Schlemms Cannal

Rat

Rabbit

Accommodation

Ciliary Muscle

Tapetum Lucidum

Eye Shine Canine

Nontapetal

Tapetal

Tapetal

Retina Fundus

Canine

Primate

Rabbit: Merangiotic

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 Dog

Rat: No Lamina Cribrosa