Glaucoma, Ocular Hypertension (intraocular pressure, IOP)

Summary: Induced elevation of IOP is widely used as an experimental approach to mimic glaucoma pathology in animals.

Model Description

Glaucoma is a group of neurodegenerative diseases. The principal features of glaucoma are: irreversible damage of optic nerve axons, death of retinal ganglion cells (RGCs) and loss of visual field. The exact mechanism of axonal damage is still unknown, although an increased intraocular pressure (IOP) is considered the major causative factor leading to pathological structural and functional changes. Induced elevation of IOP is widely used as an experimental approach to mimic glaucoma pathology in animals. Increase in the IOP level has been shown to lead to rapid and significant RGC loss and optic nerve damage. Previously reported (John et al., 1998; Kaja et al., 2014) DBA/2J mouse show inherited, age-related progression of glaucomatous pathology. 

Animal speciesRats, mice and rabbits (IOP-related studies)
Method of induction1. Argon laser application to episcleral veins (6-8 months old rats)
2. Polystyrene bead injection into anterior chamber (rats and mice, independent of age)
3. IOP measurements in normotensive eyes (rabbits)
4. DBA/2J mouse (The Jackson laboratories)
Follow-up periodRats: at least 2 weeks (typically 2-4 weeks)
Mice: at least 6 weeks
DBA/2J: 8-10 months (6-16 months of age)
Route of compound administrationTopical (e.g. eye drops), intravitreal injections, systemic (i.v., i.p.), subcutaneous
Read-outs1. In vivo imaging:
– Optical coherence tomography
2. In vivo functional assessment:
– Electroretinography
– Visual evoked potentials
3. Slit-lamp, ophthalmoscopic examination
4. Morphological assessment:
– Optic nerve axon counts (semi-thin optic nerve sections)
– Routine histology (H&E staining for retinal sections)
– Immunohistochemistry (typically RGC marker/glial marker and counterstain in retinal wholemounts),
– Stereology of RGCs (retinal wholemounts) and optic nerve axons
5. Molecular biology (ELISA, Western blotting, qPCR)

Outcomes and Read-Outs 

In vivo imaging

StereologyTotal numbers of retinal ganglion cells from retinal wholemounts and optic nerve axons from semi-thin optic nerve sections are estimated using unbiased stereology (StereoInvestigator, MBF Bioscience, Inc.) 

Fig. 1. Semi-thin sections of rat optic nerve.
Fig. 1. Semi-thin sections of rat optic nerve. Black arrows in the image from the control eye optic nerve cross-section point to optic nerve axons. White arrows in the picture from laser-induced model indicate degenerated axons. Scale bar = 20 µm. 

Authors' picture