HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Machida, S. Articles by Bush, R. A. Search for Related Content PubMed PubMed Citation Articles by Machida, S. Articles by Bush, R. A.

Photopic ERG Negative Response from Amacrine Cell Signaling in RCS Rat Retinal Degeneration

¹From the Department of Ophthalmology, Iwate Medical University School of Medicine, Iwate, Japan; ³Section for Translational Research in Retinal and Macular Degeneration, National Institute on Deafness and Other Communication Disorders, National Institutes of Health (NIH), Bethesda, Maryland; and ⁴Biological Imaging Core, National Eye Institute, NIH, Bethesda, Maryland.

PURPOSE. The authors investigated photopic electroretinographic changes during degeneration in the Royal College of Surgeons (RCS) and transgenic P23H rhodopsin rat models, including the cellular origins of a large corneal-negative component that persists in the RCS rat.

METHODS. Photopic and scotopic electroretinograms (ERGs) were recorded from dystrophic RCS (RCS-p⁺/Lav) rats (4–18 weeks old) and transgenic rhodopsin Pro23His line 1 (P23H) rats (4–30 weeks old). Age-matched congenic (RCS-rdy⁺p⁺/Lav) and Sprague-Dawley rats were used as controls. N-methyl-DL-aspartic acid (NMA), dopamine, and -aminobutyric acid (GABA) were injected intravitreally, and optic nerve sectioning (ONS) was performed to suppress or remove inner retinal neuron activity. Retinal morphology for cone cell counts and immunohistochemistry for quantification of Kir4.1 channels were performed at various stages of degeneration.

RESULTS. As degeneration progressed, the photopic ERG of RCS dystrophic rats was distinctly different from that of P23H rats, primarily because of the growth of a corneal-negative response (RCS-NPR) after the b-wave in RCS rats. This response had a peak time similar to the photopic negative response (PhNR) in controls but with a more gradual recovery phase, and it was not affected by ONS. The PhNR in P23H rats declined linearly with the b-wave. NMA and GABA eliminated the RCS-NPR and uncovered a larger b-wave in RCS rats at late stages of degeneration, but NMA had little effect on the ERG in P23H rats. The NMA-sensitive negative response in RCS rats declined with age more slowly than did the NMA-isolated b-wave. The density of Kir4.1 channels at the endfeet of Müller cells and in the proximal retina increased significantly between 6 to 10 weeks and 14 weeks of age in the RCS rat retina but not in the P23H rat retina.

CONCLUSIONS. The photopic ERG of the dystrophic RCS rat retina becomes increasingly electronegative because of an aberrant negative response, originating from amacrine cell activity, which declines more slowly than the b-wave with degeneration. The absence of this response in the P23H rat indicates that the inner retinal cone pathway pathology is different in the two models. A relative increase in Kir4.1 channels on Müller cells of RCS retina may contribute to the enhanced negative ERG response in the RCS rat.

This article has been cited by other articles:

				D. K. Mojumder, D. M. Sherry, and L. J. Frishman Contribution of voltage-gated sodium channels to the b-wave of the mammalian flash electroretinogram J. Physiol., May 15, 2008; 586(10): 2551 - 2580. [Abstract] [Full Text] [PDF]