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Mapping cation entry in photoreceptors and inner retinal neurons during early degeneration in the P23H-3 rat retina

Published online by Cambridge University Press:  05 April 2013

YUAN ZHU
Affiliation:
School of Optometry and Vision Science, University of New South Wales, Sydney, Australia
STUTI MISTRA
Affiliation:
Department of Optometry and Vision Science, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand
LISA NIVISON-SMITH
Affiliation:
School of Optometry and Vision Science, University of New South Wales, Sydney, Australia
MONICA L. ACOSTA
Affiliation:
Department of Optometry and Vision Science, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand
ERICA L. FLETCHER
Affiliation:
Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Australia
MICHAEL KALLONIATIS*
Affiliation:
School of Optometry and Vision Science, University of New South Wales, Sydney, Australia Department of Optometry and Vision Science, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Australia Centre for Eye Health, University of New South Wales, Sydney, Australia
*
*Address correspondence to: Prof. Michael Kalloniatis, Centre for Eye Health, University of New South Wales, Sydney 2052, NSW, Australia. E-mail: [email protected]

Abstract

The proline-23-histidine line 3 (P23H-3) transgenic rat carries a human opsin gene mutation leading to progressive photoreceptor loss characteristic of human autosomal dominant retinitis pigmentosa. The aim of the present study was to evaluate neurochemical modifications in the P23H-3 retina as a function of development and degeneration. Specifically, we investigated the ion channel permeability of photoreceptors by tracking an organic cation, agmatine (1-amino-4-guanidobutane, AGB), which permeates through nonspecific cation channels. We also investigated the activity of ionotropic glutamate receptors in distinct populations of bipolar, amacrine, and ganglion cells using AGB tracking in combination with macromolecular markers. We found elevated cation channel permeation in photoreceptors as early as postnatal day 12 (P12) suggesting that AGB labeling is an early indicator of impending photoreceptor degeneration. However, bipolar, amacrine, or ganglion cells displayed normal responses secondary to ionotropic glutamate receptor activation even at P138 when about one half of the photoreceptor layer was lost and apoptosis and gliosis were observed. These results suggest that possible therapeutic windows as downstream neurons in inner retina appear to retain normal function with regard to AGB permeation when photoreceptors are significantly reduced but not lost.

Type
Research Articles
Copyright
Copyright © Cambridge University Press 2013 

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