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      Effect of a Nitric Oxide Synthase Inhibitor on Lens-Induced Myopia

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          Abstract

          Purpose: It has still not been determined whether the retinal mechanism causing form-deprivation myopia (FDM) is different from that causing lens-induced myopia (LIM). We previously reported that FDM was blocked by an intravitreal injection of the nitric oxide (NO) synthase inhibitor, N-nitro- L-arginine methyl ester ( L-NAME). In this study, we investigated the effect of L-NAME on LIM in chicks. Method: The left eyes of 6-day-old chicks were injected with 30 µl of nontoxic concentrations of L-NAME (≤360 m M) or saline. The right eyes were injected with 30 µl of saline. A –16 dpt lens was placed in front of the left eye for 6 days. Another group of 6 chicks were injected with 180 m M L-NAME (left eye) and with saline (right eye) before placing –16 dpt lenses in front of both eyes. After removing the lens, the refraction and the axial length were measured. The effect of L-NAME (180 m M) on the retina of a separate group of chicks was examined by electroretinography 60 min after an intravitreal injection in non-LIM-treated eyes. Results: The eyes of chicks that were injected with 180 or 360 m M L-NAME were less myopic and had significantly shorter axial lengths than control eyes. A significant decrease of the On response and an increase of the Off response were observed. Conclusion: The injection of L-NAME into developing chick eyes that were then covered with a –16 dpt lens resulted in a modifications of retinal function and an inhibition of the development of myopia. These results, combined with the earlier findings, suggest that NO modulates a common retinal pathway that leads to both LIM and FDM.

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          Moving the retina: Choroidal modulation of refractive state

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            The localization of nitric oxide synthase in the rat eye and related cranial ganglia.

            Nitric oxide synthase is the biosynthetic enzyme for the free radical neurotransmitter nitric oxide. Using an affinity-purified antiserum, nitric oxide synthase was found to be localized to peripheral ocular nerve fibers, related cranial ganglia, and the retina of the rat. In the eye, nitric oxide synthase-like immunoreactive peripheral nerve fibers were visualized mainly in the choroid and about limbal blood vessels. The anterior uvea was quite sparsely innervated, and the cornea was negative. Many principal neurons in the pterygopalatine ganglion were immunoreactive for nitric oxide synthase while very few cells stained in the superior cervical and trigeminal ganglia. Virtually all nitric oxide synthase-like immunoreactive pterygopalatine cells were also immunostained for vasoactive intestinal polypeptide; nitric oxide synthase also partially co-localized with neuropeptide Y in some of the neurons of this ganglion. Pterygopalatine ganglionectomy significantly reduced the number of peripheral nitric oxide synthase-like immunoreactive nerve fibers in the eye. A variety of immunoreactive retinal cells were seen. Most cells in the inner nuclear layer or ganglion cell layer corresponded morphologically to amacrine cells and displaced amacrine cells. Interplexiform cells and occasional faintly stained cells in the outer portion of the inner nuclear layer also were visualized. Nicotinamide adenine dinucleotide phosphate diaphorase histochemistry generally stained cells of similar distribution but did reveal somewhat more extensive localizations in peripheral ocular tissues, the ciliary ganglion, and the retina, compared with nitric oxide synthase immunohistochemistry. Nitric oxide synthase thus localizes to peripheral ocular nerve fibers, chiefly parasympathetic in nature and derived from the pterygopalatine ganglion, and to several cell types in the retina. Nitric oxide probably acts as a choroidal vasodilator of parasympathetic origin in the eye; the neuropeptide co-localizations in the pterygopalatine ganglion suggest complex neuromodulatory interactions. The retinal localizations imply potential neurotransmitter functions for nitric oxide in this tissue.
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              Properties of the feedback loops controlling eye growth and refractive state in the chicken

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                Author and article information

                Journal
                ORE
                Ophthalmic Res
                10.1159/issn.0030-3747
                Ophthalmic Research
                S. Karger AG
                0030-3747
                1423-0259
                2001
                April 2001
                05 March 2001
                : 33
                : 2
                : 75-79
                Affiliations
                Departments of aApplied Medical Engineering and bOphthalmology, Osaka University Graduate School of Medicine, Osaka, Japan
                Article
                55647 Ophthalmic Res 2001;33:75–79
                10.1159/000055647
                11244351
                20e21aaf-e57c-455c-b8ea-0054a8ccd1dc
                © 2001 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 3, References: 16, Pages: 5
                Categories
                Original Paper

                Vision sciences,Ophthalmology & Optometry,Pathology
                Electroretinography,Chick,Experimental myopia,Nitric oxide,Lens-induced myopia

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