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(Investigative Ophthalmology and Visual Science. 2003;44:3933-3946.)
© 2003 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.02-0774

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GABA, Experimental Myopia, and Ocular Growth in Chick

Richard A. Stone,1 Ji Liu,1 Reiko Sugimoto,1,2 Cheryl Capehart,1 Xiaosong Zhu,1,3 and Klara Pendrak1

1From the Department of Ophthalmology, University of Pennsylvania, School of Medicine, Scheie Eye Institute, Philadelphia, Pennsylvania.

PURPOSE. To learn whether {gamma}-aminobutyric acid (GABA) participates in retinal mechanisms that influence refractive development.

METHODS. White leghorn chicks, some of which wore a unilateral goggle to induce myopia, received daily intravitreal injections of agonists or antagonists to the major GABA receptor subtypes. Eyes were studied with refractometry, ultrasound, and calipers. Retinas of other chicks wearing unilateral goggles were assayed for GABA content.

RESULTS. Antagonists to GABAA or GABAA0r (formerly known as GABAC) receptors inhibited form-deprivation myopia. GABAA antagonists showed greater inhibition of myopic growth in the equatorial than the axial dimension. A GABAA0r antagonist displayed parallel inhibition in the axial and equatorial dimensions. A GABAA0r agonist but not GABAA agonists altered the myopic refraction of goggled eyes. GABAB receptor antagonists, more so than an agonist, also slowed development of myopia, inhibiting axial growth more effectively than equatorial expansion of goggled eyes. When administered to nongoggled eyes, GABAA or GABAA0r agonists or antagonists also altered eye growth, chiefly stimulating it. Only a GABAA agonist induced a myopic refraction. Several of these agents stimulated eye growth in the axial, but not the equatorial, dimension. Retinal GABA content was slightly reduced in goggled eyes.

CONCLUSIONS. GABAA, GABAA0r, and GABAB receptors modulate eye growth and refractive development. The anatomic effects of these drugs reinforce the notion that eye shape and not just eye size is regulated. A retinal site of action is consistent with the known ocular localizations of GABA and its receptors and with the altered retinal biochemistry in form-deprived eyes.





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