GABA, experimental myopia, and ocular growth in chick.
OBJECTIVE
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 GABA(A) or GABA(A0r) (formerly known as GABA(C)) receptors inhibited form-deprivation myopia. GABA(A) antagonists showed greater inhibition of myopic growth in the equatorial than the axial dimension. A GABA(A0r) antagonist displayed parallel inhibition in the axial and equatorial dimensions. A GABA(A0r) agonist but not GABA(A) agonists altered the myopic refraction of goggled eyes. GABA(B) 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, GABA(A) or GABA(A0r) agonists or antagonists also altered eye growth, chiefly stimulating it. Only a GABA(A) 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
GABA(A), GABA(A0r), and GABA(B) 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.
Stone
Richard A
RA
Department of Ophthalmology, University of Pennsylvania, School of Medicine, Scheie Eye Institute, Philadelphia, Pennsylvania 19104, USA. stone@mail.med.upenn.edu
Liu
Ji
J
Sugimoto
Reiko
R
Capehart
Cheryl
C
Zhu
Xiaosong
X
Pendrak
Klara
K
D000818:Animals; D002645:Chickens; D004195:Disease Models, Animal; D005123:Eye / Q000187:drug effects / Q000254:growth & development*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D009216:Myopia / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D018079:Receptors, GABA / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D012160:Retina / Q000187:drug effects / Q000502:physiology; D012683:Sensory Deprivation; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; C087200:GABA-C receptor; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid