Summary: Induced elevation of IOP is widely used as an experimental approach to mimic glaucoma pathology in animals.
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 species||Rats, mice and rabbits (IOP-related studies)|
|Method of induction||1. 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)
5. Poly(acrilic acid) injection into anterior chamber
|Follow-up period||Rats: 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 administration||Topical (e.g. eye drops), intravitreal injections, systemic (i.v., i.p.), subcutaneous|
|Read-outs||1. In vivo imaging:|
– Optical coherence tomography
2. In vivo functional assessment:
– 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
- Kaja S, Naumchuk Y, Grillo SL, Borden PK, Koulen P (2014). Differential up-regulation of Vesl-1/Homer 1 protein isoforms associated with decline in visual performance in a preclinical glaucoma model. Vision Res. 94:16-23.
- Kalesnykas G, Oglesby EN, Zack DJ, Cone FE, Steinhart MR, Tian J, Pease ME, Quigley HA (2012) Retinal ganglion cell morphology after optic nerve crush and experimental glaucoma. Invest Ophthalmol Vis Sci 53: 3847-3857.
- Kalesnykas G, Niittykoski M, Rantala J, Miettinen R, Salminen A, et al. (2007a). The expression of heat shock protein 27 in retinal ganglion and glial cells in a rat glaucoma model. Neuroscience 150: 692-704.
- Kalesnykas G & Uusitalo H (2007b) Comparison of simultaneous readings of intraocular pressure in rabbits using Perkins handheld, Tono-Pen XL, and TonoVet tonometers. Graefes Arch Clin Exp Ophthalmol 245:761-762.
- John SW, Smith RS, Savinova OV, Hawes NL, Chang B, Turnbull D, Davisson M, Roderick TH, Heckenlively JR. Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice. Invest Ophthalmol Vis Sci. 1998 May;39(6):951-62. Erratum in: Invest Ophthalmol Vis Sci 1998 Aug;39(9):1641.