Anterograde Transport in Axons of the Retinal Ganglion Cells and its Relationship to the Intraocular Pressure during Aging in Mice with Hereditary Pigmentary Glaucoma

ABSTRACT

Purpose: To establish a relationship between impairment of the anterograde axonal transport (AAT) in the axons of the retinal ganglion cells and the intraocular pressure (IOP) during aging in mice with hereditary glaucoma.

Methods: Quantitative in vivo approach based on manganese enhanced magnetic resonance imaging was developed in order to evaluate AAT in 3-, 6-, and 14-month old DBA/2J mice that develop age-dependent pigmentary glaucoma or age-matched C57Bl/6 mice that do not develop any retinal disease. Unilateral intravitreous administration of MnCl₂ solution was followed 24 h later by MRI performed to obtain spin-lattice relaxation times (T₁) for regions of interest encompassing the superior colliculi (SC) and the lateral geniculate nuclei (LGN). From the MRI scans, the estimates of Mn²⁺ concentrations in SC and LGN contralateral to the injection site, hence the efficiency of AAT in ON, were obtained. IOP and eye morphology was also monitored.

Results: In C57Bl/6 mice, AAT to SC was decreasing with age, 30% decrease was noted between 3 and 14 months. The decrease in axonal transport to LGN was less pronounced in this strain. In 3-month-old DBA/2J mice, axonal transport to SC was 30% lower than in 3-month-old C57Bl/6 mice but no significant decrease was noted in 6-month-old animals. However, a decrease of over 95% in axonal transport both to SC and LGN was noted in 14-month-old DBA/2J mice. DBA/2J mice exhibited a sharp increase in IOP at 6 months, which reversed at 14 months but displayed age-dependent elongation of the eyeball and deepening of the anterior chamber.

Conclusion: Failure of AAT to SC of DBA/2J mice during development of pigmentary glaucoma does not follow closely changes in IOP and eye morphology. The relationship between IOP and AAT in optic nerve and tract is complex and may reflect preconditioning mechanism.

KEYWORDS:

• Glaucoma
• manganese-enhanced magnetic resonance imaging
• MEMRI
• extra-retinal degeneration
• visual pathway

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Funding

This study was supported by Polish National Science Centre grant (DEC-2012/07/D/NZ4/04199) to MF. Project carried out with the use of CePT infrastructure financed by the European Union – the European Regional Development Found in the Operational Program “Innovative Economy” for 2007–2013.