Specific amacrine cell changes in an induced mouse model of glaucoma

Authors

  • David J Gunn MBBS(Hons),

    1. The University of Queensland, Perinatal Research Centre
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  • Glen A Gole FRANZCO MD,

    1. The University of Queensland, Discipline of Paediatrics and Child Health
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  • Nigel L Barnett DPhil

    Corresponding author
    1. The University of Queensland, Perinatal Research Centre
    2. The University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, Australia
      Dr Nigel L Barnett, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Herston, Qld 4029, Australia. Email: n.barnett@uq.edu.au
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Dr Nigel L Barnett, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Herston, Qld 4029, Australia. Email: n.barnett@uq.edu.au

Abstract

Background:  To investigate retinal cell population changes under chronic elevated intraocular pressure in an inducible mouse model of glaucoma.

Methods:  Chronic unilateral ocular hypertension was induced in 40 C57BL6/J mice by ablation of the limbal episcleral veins. After 5, 20, 40 and 60 days of elevated intraocular pressure, specific retinal cell types were identified and/or quantified by immunohistochemistry for protein kinase C α, glial fibrillary acidic protein, parvalbumin and calretinin. Apoptotic cells were identified by TUNEL and cleaved caspase-3 immunohistochemistry.

Results:  Elevations in intraocular pressure in the range 22–30 mmHg were developed and sustained in mice for up to 60 days. Protein kinase C α immunoreactivity localized to bipolar cells was unchanged. We observed a rapid increase in glial fibrillary acidic protein expression in Müller cells and a progressive loss of parvalbumin-labelled ganglion cells. After 60 days of elevated intraocular pressure, calretinin-immunoreactive cell counts declined by 55.4% and 46.4% in the inner nuclear and ganglion cell layers, respectively. However, at all time points examined, the markers of cell death were only observed in the ganglion cell layer, not in the inner nuclear layer.

Conclusions:  In addition to ganglion cell death and reactive Müller cell changes, chronic experimental elevation of intraocular pressure alters calcium-binding protein immunohistochemistry in amacrine cells. However, these changes are not indicative of amacrine cell loss but may represent early indicators of cellular distress that precede physiological dysfunction or cell death.

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