Abstract
Abstract: :
Purpose: The excitotoxin quisqualic acid (QA) injected into the chicken eye is known to destroy many amacrine cells while deprivation myopia can still be induced. Glucagon immunoreactive amacrine cells are largely unaffected by QA treatment suggesting them as potential elements in the pathway of eye growth control. We have studied (1) whether chick eyes still respond to negative and positive defocus 6 days after QA application, (2) whether, under the same conditions, expression of the transcription factor ZENK in glucagon amacrine cells still remains sign-of-defocus-selective. Methods: Chicks were intravitreally injected with 200 nmol QA in one eye. Contralateral eyes received saline injections. After 6 days, chicks were binocularly treated with either +7 D or -7 D lenses and divided in 2 groups: (1) Lenses were left on for 4 days, refractions were measured at the beginning and at the end of the treatment. (2) After 2 hours of lens wear, ZENK- and glucagon-IR amacrine cells were counted in double-labeled transversal cryostat sections of the retina. Toluidin blue staining was used to control effects of QA on gross retinal morphology. Results: (1) QA treatment reduced the thickness of both IPL and INL and the density in the ganglion cell layer. (2) QA-injected eyes all became myopic no matter if they wore positive or negative lenses whereas saline injected control eyes grew into the right directions: -3.2 ± 4.3 D in QA eyes vs 5.3 ± 0.9 D in saline eyes, p = 0.004 for +7 D and -7.1 ± 3.2 D vs -2.3 ± 0.8 D, p = 0.01 for -7 D. (3) ZENK expression was downregulated in all QA-injected eyes and in saline-injected control eyes wearing -7 D lenses, but upregulated in saline-injected control eyes wearing +7 D lenses (QA- vs saline-injected eyes: p = 0.002 for +7 D, p = 0.008 for -7 D ). Conclusion: Both refractions and ZENK expression suggest that the retina may no longer be able to detect the sign of defocus after QA treatment but rather generates myopia with both lens types. It is also possible that QA treatment moves the set-point of emmetropization to a more myopic baseline with reduced ZENK expression.
Keywords: 481 myopia • 557 retina: proximal(bipolar, amacrine, and ganglion cells) • 514 pharmacology