Optic nerve head axonal transport in rabbits with hereditary glaucoma

Area of Science:

• Ophthalmology
• Genetics
• Neuroscience

Background:

• Hereditary glaucoma in rabbits (bu/bu) mimics human congenital glaucoma and buphthalmia.
• Previous research on albino bu/bu rabbits was limited by poor health and breeding.
• Pigmented bu/bu rabbits were bred to improve hardiness and create a better disease model.

Purpose of the Study:

• To investigate the role of mechanical factors in optic nerve head (ONH) pathology in rabbits with hereditary glaucoma.
• To evaluate orthograde axonal transport in the ONH of bu/bu rabbits with varying intraocular pressure (IOP).

Main Methods:

• Breeding of pigmented bu/bu rabbits to establish a more robust model.
• Measurement of intraocular pressure (IOP) in newborn and adult bu/bu rabbits.
• Intravitreal injection of [3H]leucine to trace orthograde axonal transport.
• Light- and electron-microscopic radioautography of the optic nerve head (ONH) and superior colliculi.

Main Results:

• Pigmented bu/bu rabbits exhibited high mortality, similar to albino counterparts.
• Newborn bu/bu rabbits had normal IOP, which increased significantly by 1-3 months, then normalized after 6-10 months.
• Elevated IOP in bu/bu rabbits caused small zones of axonal transport blockage adjacent to ONH connective tissue beams.
• Unlike monkeys and cats, rabbits (lacking a true lamina cribrosa) showed no marked blockage of axonal transport during acute IOP elevation.
• Chronic IOP elevation in bu/bu rabbits did not lead to significant optic axon loss, but caused some optic nerve terminal degeneration in the superior colliculi.

Conclusions:

• The rabbit's unique ONH anatomy, lacking a true lamina cribrosa, appears protective against severe axonal transport disruption and optic nerve damage during elevated IOP.
• Results support the mechanical theory of ONH damage in glaucoma.
• Further research is needed to fully elucidate the mechanisms of optic nerve damage in glaucoma models.