Alterations in ZENK and glucagon RNA transcript expression during increased ocular growth in chickens

Regan Ashby, Peter Kozulin, Pam L. Megaw, Ian G. Morgan

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Purpose: To examine in detail the time-course of changes in Zif268, Egr-1, NGFI-A, and Krox-24 (ZENK) and pre-proglucagon (PPG) RNA transcript levels in the chick retina during periods of increased ocular growth induced by form-deprivation and negative-lens wear. To further elucidate the role of ZENK in the modulation of ocular growth, we investigated the effect of intravitreal injections of the muscarinic antagonist atropine and the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN), both of which block the development of experimental myopia, on the expression of ZENK in eyes fitted with negative-lenses. Methods: Myopia was induced by fitting translucent diffusers or -10D polymethyl methacrylate (PMMA) lenses over one eye of the chicken. At times from 1 h to 10 days after fitting of the diffusers or negative lenses, retinal RNA transcript levels of the selected genes were determined by semi-quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). For the pharmacology experiments, -10D lenses were fitted over the left eye of chicks for a period of 1h. Intravitreal injections of atropine (10 μl-25 mM), ADTN (10 μl-10 mM), or a vehicle solution were made immediately before fitting of the lenses. Results: ZENK RNA transcript levels were rapidly and persistently down-regulated following the attachment of the optical devices over the eye. With a delay relative to ZENK, PPG transcript levels were also down-regulated. Induced changes in gene expression were similar for both form-deprivation and negative-lens wear. When atropine or ADTN were administered immediately before lens attachment, the rapid down-regulation in ZENK RNA transcript levels normally seen following 1 h of negative-lens wear was not seen, and ZENK transcript levels rose above those values seen in control eyes. However, injection of atropine or ADTN into untreated eyes had no effect on ZENK transcript levels. Conclusions: Both form-deprivation and negative-lens wear modulated the retinal expression of ZENK and PPG RNA transcripts, with a similar time-course and strength of response. The ability of the tested drugs to prevent the down-regulation of ZENK in both lens-induced myopia (LIM) and form-deprivation myopia (FDM) suggests that atropine and ADTN act directly and rapidly on retinal circuits to enhance sensitivity early in the signaling process. These findings suggest that very similar molecular pathways are involved in the changes in eye growth in response to form-deprivation and negative lenses at 1 h after the fitting of optical devices.

Original languageEnglish
Pages (from-to)639-649
Number of pages11
JournalMolecular Vision
Volume16
Publication statusPublished - 13 Apr 2010
Externally publishedYes

Fingerprint

Glucagon
Lenses
Chickens
RNA
Growth
Atropine
Proglucagon
Myopia
Optical Devices
Intravitreal Injections
Down-Regulation
Muscarinic Antagonists
Dopamine Agonists
Polymethyl Methacrylate
Reverse Transcriptase Polymerase Chain Reaction
Retina
ADTN
Real-Time Polymerase Chain Reaction
Pharmacology
Gene Expression

Cite this

Ashby, Regan ; Kozulin, Peter ; Megaw, Pam L. ; Morgan, Ian G. / Alterations in ZENK and glucagon RNA transcript expression during increased ocular growth in chickens. In: Molecular Vision. 2010 ; Vol. 16. pp. 639-649.
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title = "Alterations in ZENK and glucagon RNA transcript expression during increased ocular growth in chickens",
abstract = "Purpose: To examine in detail the time-course of changes in Zif268, Egr-1, NGFI-A, and Krox-24 (ZENK) and pre-proglucagon (PPG) RNA transcript levels in the chick retina during periods of increased ocular growth induced by form-deprivation and negative-lens wear. To further elucidate the role of ZENK in the modulation of ocular growth, we investigated the effect of intravitreal injections of the muscarinic antagonist atropine and the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN), both of which block the development of experimental myopia, on the expression of ZENK in eyes fitted with negative-lenses. Methods: Myopia was induced by fitting translucent diffusers or -10D polymethyl methacrylate (PMMA) lenses over one eye of the chicken. At times from 1 h to 10 days after fitting of the diffusers or negative lenses, retinal RNA transcript levels of the selected genes were determined by semi-quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). For the pharmacology experiments, -10D lenses were fitted over the left eye of chicks for a period of 1h. Intravitreal injections of atropine (10 μl-25 mM), ADTN (10 μl-10 mM), or a vehicle solution were made immediately before fitting of the lenses. Results: ZENK RNA transcript levels were rapidly and persistently down-regulated following the attachment of the optical devices over the eye. With a delay relative to ZENK, PPG transcript levels were also down-regulated. Induced changes in gene expression were similar for both form-deprivation and negative-lens wear. When atropine or ADTN were administered immediately before lens attachment, the rapid down-regulation in ZENK RNA transcript levels normally seen following 1 h of negative-lens wear was not seen, and ZENK transcript levels rose above those values seen in control eyes. However, injection of atropine or ADTN into untreated eyes had no effect on ZENK transcript levels. Conclusions: Both form-deprivation and negative-lens wear modulated the retinal expression of ZENK and PPG RNA transcripts, with a similar time-course and strength of response. The ability of the tested drugs to prevent the down-regulation of ZENK in both lens-induced myopia (LIM) and form-deprivation myopia (FDM) suggests that atropine and ADTN act directly and rapidly on retinal circuits to enhance sensitivity early in the signaling process. These findings suggest that very similar molecular pathways are involved in the changes in eye growth in response to form-deprivation and negative lenses at 1 h after the fitting of optical devices.",
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Alterations in ZENK and glucagon RNA transcript expression during increased ocular growth in chickens. / Ashby, Regan; Kozulin, Peter; Megaw, Pam L.; Morgan, Ian G.

In: Molecular Vision, Vol. 16, 13.04.2010, p. 639-649.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alterations in ZENK and glucagon RNA transcript expression during increased ocular growth in chickens

AU - Ashby, Regan

AU - Kozulin, Peter

AU - Megaw, Pam L.

AU - Morgan, Ian G.

PY - 2010/4/13

Y1 - 2010/4/13

N2 - Purpose: To examine in detail the time-course of changes in Zif268, Egr-1, NGFI-A, and Krox-24 (ZENK) and pre-proglucagon (PPG) RNA transcript levels in the chick retina during periods of increased ocular growth induced by form-deprivation and negative-lens wear. To further elucidate the role of ZENK in the modulation of ocular growth, we investigated the effect of intravitreal injections of the muscarinic antagonist atropine and the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN), both of which block the development of experimental myopia, on the expression of ZENK in eyes fitted with negative-lenses. Methods: Myopia was induced by fitting translucent diffusers or -10D polymethyl methacrylate (PMMA) lenses over one eye of the chicken. At times from 1 h to 10 days after fitting of the diffusers or negative lenses, retinal RNA transcript levels of the selected genes were determined by semi-quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). For the pharmacology experiments, -10D lenses were fitted over the left eye of chicks for a period of 1h. Intravitreal injections of atropine (10 μl-25 mM), ADTN (10 μl-10 mM), or a vehicle solution were made immediately before fitting of the lenses. Results: ZENK RNA transcript levels were rapidly and persistently down-regulated following the attachment of the optical devices over the eye. With a delay relative to ZENK, PPG transcript levels were also down-regulated. Induced changes in gene expression were similar for both form-deprivation and negative-lens wear. When atropine or ADTN were administered immediately before lens attachment, the rapid down-regulation in ZENK RNA transcript levels normally seen following 1 h of negative-lens wear was not seen, and ZENK transcript levels rose above those values seen in control eyes. However, injection of atropine or ADTN into untreated eyes had no effect on ZENK transcript levels. Conclusions: Both form-deprivation and negative-lens wear modulated the retinal expression of ZENK and PPG RNA transcripts, with a similar time-course and strength of response. The ability of the tested drugs to prevent the down-regulation of ZENK in both lens-induced myopia (LIM) and form-deprivation myopia (FDM) suggests that atropine and ADTN act directly and rapidly on retinal circuits to enhance sensitivity early in the signaling process. These findings suggest that very similar molecular pathways are involved in the changes in eye growth in response to form-deprivation and negative lenses at 1 h after the fitting of optical devices.

AB - Purpose: To examine in detail the time-course of changes in Zif268, Egr-1, NGFI-A, and Krox-24 (ZENK) and pre-proglucagon (PPG) RNA transcript levels in the chick retina during periods of increased ocular growth induced by form-deprivation and negative-lens wear. To further elucidate the role of ZENK in the modulation of ocular growth, we investigated the effect of intravitreal injections of the muscarinic antagonist atropine and the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN), both of which block the development of experimental myopia, on the expression of ZENK in eyes fitted with negative-lenses. Methods: Myopia was induced by fitting translucent diffusers or -10D polymethyl methacrylate (PMMA) lenses over one eye of the chicken. At times from 1 h to 10 days after fitting of the diffusers or negative lenses, retinal RNA transcript levels of the selected genes were determined by semi-quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). For the pharmacology experiments, -10D lenses were fitted over the left eye of chicks for a period of 1h. Intravitreal injections of atropine (10 μl-25 mM), ADTN (10 μl-10 mM), or a vehicle solution were made immediately before fitting of the lenses. Results: ZENK RNA transcript levels were rapidly and persistently down-regulated following the attachment of the optical devices over the eye. With a delay relative to ZENK, PPG transcript levels were also down-regulated. Induced changes in gene expression were similar for both form-deprivation and negative-lens wear. When atropine or ADTN were administered immediately before lens attachment, the rapid down-regulation in ZENK RNA transcript levels normally seen following 1 h of negative-lens wear was not seen, and ZENK transcript levels rose above those values seen in control eyes. However, injection of atropine or ADTN into untreated eyes had no effect on ZENK transcript levels. Conclusions: Both form-deprivation and negative-lens wear modulated the retinal expression of ZENK and PPG RNA transcripts, with a similar time-course and strength of response. The ability of the tested drugs to prevent the down-regulation of ZENK in both lens-induced myopia (LIM) and form-deprivation myopia (FDM) suggests that atropine and ADTN act directly and rapidly on retinal circuits to enhance sensitivity early in the signaling process. These findings suggest that very similar molecular pathways are involved in the changes in eye growth in response to form-deprivation and negative lenses at 1 h after the fitting of optical devices.

KW - Egr1

KW - Glucagon

KW - ZENK

KW - Retina

KW - Myopia

KW - Axial length

KW - Refractive error

KW - Refraction

KW - Gene expression

KW - Chicken

UR - http://www.molvis.org/molvis/volume16.html

M3 - Article

VL - 16

SP - 639

EP - 649

JO - Molecular Vision

JF - Molecular Vision

SN - 1090-0535

ER -