Specific amacrine cell changes in an induced mouse model of glaucoma

David J. Gunn, Glen A. Gole, Nigel L. Barnett

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

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 60days 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 22-30mmHg were developed and sustained in mice for up to 60days. 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 60days 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.

Original languageEnglish
Pages (from-to)555-563
Number of pages9
JournalClinical and Experimental Ophthalmology
Volume39
Issue number6
DOIs
Publication statusPublished - 1 Aug 2011
Externally publishedYes

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Amacrine Cells
Glaucoma
Intraocular Pressure
Ganglia
Calbindin 2
Parvalbumins
Cell Death
Immunohistochemistry
Glial Fibrillary Acidic Protein
Protein Kinase C
Ocular Hypertension
Calcium-Binding Proteins
In Situ Nick-End Labeling
Caspase 3
Veins
Cell Count

Cite this

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title = "Specific amacrine cell changes in an induced mouse model of glaucoma",
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 60days 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 22-30mmHg were developed and sustained in mice for up to 60days. Protein kinase C α immunoreactivity localized to bipolar cells was unchanged. We observed a rapid increase in glial fibrillary acidic protein expression in M{\"u}ller cells and a progressive loss of parvalbumin-labelled ganglion cells. After 60days 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 M{\"u}ller 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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Specific amacrine cell changes in an induced mouse model of glaucoma. / Gunn, David J.; Gole, Glen A.; Barnett, Nigel L.

In: Clinical and Experimental Ophthalmology, Vol. 39, No. 6, 01.08.2011, p. 555-563.

Research output: Contribution to journalArticleResearchpeer-review

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