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PAX6 expression and retinal cell death in a transgenic mouse model for acute angle-closure glaucoma


Stanescu-Segall, Dinu; Birke, Kerstin; Wenzel, Andreas; Grimm, Christian; Orgul, Sorguel; Fischer, Jan A; Born, Walter; Hafezi, Farhad (2015). PAX6 expression and retinal cell death in a transgenic mouse model for acute angle-closure glaucoma. Journal of Glaucoma, 24(6):426-432.

Abstract

PURPOSE: PAX6 is a highly conserved protein essential for the control of eye development both in invertebrates and vertebrates. PAX6 expression persists in the adult inner retina, but little is known about its functions after completion of retinal differentiation. Therefore, we investigated PAX6 expression in wild-type and calcitonin receptor-like receptor transgenic (CLR) mice with angle-closure glaucoma.
METHODS: Intraocular pressure was measured by indentation tonometry in anesthetized mice. Eyes of mice of both genotypes were enucleated at various ages and retinas were processed for morphological analysis and PAX6 immunostaining. The content of PAX6 in retinal extracts was estimated by Western blot analysis. Retinal expression of glaucoma-related genes was analyzed by reverse transcription-polymerase chain reaction.
RESULTS: Control mice showed normal retinal morphology between p22 and p428 with steady PAX6 expression in the ganglion cell layer (GCL) and the inner nuclear layer (INL). CLR mice examined between p22 and p82 exhibited increased intraocular pressure and a progressive decrease in cell number including PAX6-expressing cells in the GCL. The INL was not affected up to postnatal day 42. Later, a significant increase in PAX6-expressing cells concomitant with an overall loss of cells was observed in the INL of CLR as compared with control mice. Retinal up-regulation of glaucoma-related genes was furthermore observed.
CONCLUSIONS: Distinctive changes of PAX6 expression in the inner retina of CLR mice suggest a role in regulatory mechanisms involved in glaucoma-related retinal cell death. The selective increase of PAX6 expression in the degenerating INL of CLR mice may represent an attempt to preserve retinal cytoarchitecture.

Abstract

PURPOSE: PAX6 is a highly conserved protein essential for the control of eye development both in invertebrates and vertebrates. PAX6 expression persists in the adult inner retina, but little is known about its functions after completion of retinal differentiation. Therefore, we investigated PAX6 expression in wild-type and calcitonin receptor-like receptor transgenic (CLR) mice with angle-closure glaucoma.
METHODS: Intraocular pressure was measured by indentation tonometry in anesthetized mice. Eyes of mice of both genotypes were enucleated at various ages and retinas were processed for morphological analysis and PAX6 immunostaining. The content of PAX6 in retinal extracts was estimated by Western blot analysis. Retinal expression of glaucoma-related genes was analyzed by reverse transcription-polymerase chain reaction.
RESULTS: Control mice showed normal retinal morphology between p22 and p428 with steady PAX6 expression in the ganglion cell layer (GCL) and the inner nuclear layer (INL). CLR mice examined between p22 and p82 exhibited increased intraocular pressure and a progressive decrease in cell number including PAX6-expressing cells in the GCL. The INL was not affected up to postnatal day 42. Later, a significant increase in PAX6-expressing cells concomitant with an overall loss of cells was observed in the INL of CLR as compared with control mice. Retinal up-regulation of glaucoma-related genes was furthermore observed.
CONCLUSIONS: Distinctive changes of PAX6 expression in the inner retina of CLR mice suggest a role in regulatory mechanisms involved in glaucoma-related retinal cell death. The selective increase of PAX6 expression in the degenerating INL of CLR mice may represent an attempt to preserve retinal cytoarchitecture.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Ophthalmology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:30 March 2015
Deposited On:16 Jul 2015 14:16
Last Modified:08 Dec 2017 13:22
Publisher:Lippincott Williams & Wilkins
ISSN:1057-0829
Additional Information:This is a non-final version of an article published in final form in Stanescu-Segall et al: PAX6 Expression and Retinal Cell Death in a Transgenic Mouse Model for Acute Angle-Closure Glaucoma, 2015, Journal of Glaucoma.
Publisher DOI:https://doi.org/10.1097/IJG.0b013e318207069b
PubMed ID:25827297

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