dc.contributor.author |
Acosta Etchebarne, Monica |
en |
dc.contributor.author |
Shin, YS |
en |
dc.contributor.author |
Ready, S |
en |
dc.contributor.author |
Fletcher, EL |
en |
dc.contributor.author |
Christie, DL |
en |
dc.contributor.author |
Kalloniatis, M |
en |
dc.date.accessioned |
2011-10-05T19:40:57Z |
en |
dc.date.issued |
2010-03-01 |
en |
dc.identifier.citation |
American Journal of Physiology Cell Physiology 298:764-774 2010 |
en |
dc.identifier.issn |
0363-6143 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/8335 |
en |
dc.description.abstract |
We determined the metabolic changes that precede cell death in the dystrophic proline-23-histidine (P23H) line 3 (P23H-3) rat retina compared with the normal SpragueDawley (SD) rat retina. Metabolite levels and metabolic enzymes were analyzed early in development and during the early stages of degeneration in the P23H-3 retina. Control and degenerating retinas showed an age-dependent change in metabolite levels and enzymatic activity, particularly around the time when phototransduction was activated. However, lactate dehydrogenase (LDH) activity was significantly higher in P23H-3 than SD retina before the onset of photoreceptor death. The creatine/phosphocreatine system did not contribute to the increase in ATP, because phosphocreatine levels, creatine kinase, and expression of the creatine transporter remained constant. However, Na+-K+-ATPase and Mg2-Ca2+-ATPase activities were increased in the developing P23H-3 retina. Therefore, photoreceptor apoptosis in the P23H-3 retina occurs in an environment of increased LDH, ATPase activity, and higher-than-normal ATP levels. We tested the effect of metabolic challenge to the retina by inhibiting monocarboxylate transport with -cyano-4-hydroxycinnamic acid or systemically administering the phosphodiesterase inhibitor sildenafil. Secondary to monocarboxylate transport inhibition, the P23H-3 retina did not demonstrate alterations in metabolic activity. However, administration of ildenafil significantly reduced LDH activity in the P23H-3 retina and increased the number of terminal deoxynucleotidyl transferase biotin-dUPT nick end-labeled photoreceptor cells. Photoreceptor cells with a rhodopsin mutation display an increase in apoptotic markers secondary to inhibition of a phototransduction enzyme phosphodiesterase), suggesting increased susceptibility to altered cation entry. |
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dc.publisher |
American Physiological Society |
en |
dc.relation.ispartofseries |
American Journal of Physiology - Cell Physiology |
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dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0363-6143/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
Retinal metabolic state of the proline-23-histidine rat model of retinitis pigmentosa |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1152/ajpcell.00253.2009 |
en |
pubs.begin-page |
764 |
en |
pubs.volume |
298 |
en |
dc.rights.holder |
Copyright: 2010 the American Physiological Society |
en |
pubs.author-url |
http://ajpcell.physiology.org/content/298/3/C764 |
en |
pubs.end-page |
774 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
190429 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Optometry and Vision Science |
en |
dc.identifier.eissn |
1522-1563 |
en |
pubs.number |
C764-C774 |
en |
pubs.record-created-at-source-date |
2010-12-03 |
en |