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X. Zhong, J. Ge, E.L. Smith III, W.K. Stell; Mechanisms of Emmetropization in Macaque: Modulation of Bipolar and Amacrine Cell Activity by Form-Deprivation and Defocus . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2804.
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Purpose: Ocular growth and refractive development are regulated by visual image quality and neural control mechanisms in the retina. Amacrine cells responsive to emmetropizing stimuli have been identified in chick by induction of the immediate-early gene products Fos and Egr-1. Here we report similar findings in a primate. Methods: Six normal rhesus monkeys, 20-30 days old and ~+3 D hyperopic, were fitted with helmets holding lenses. Half (n=3) wore a +3.00 D spectacle lens on one eye (corrected to emmetropia) and a clear plano lens over the other eye (consistently hyperopic; Hung et al., 1995); and half (n=3) wore a diffuser over one eye (no well-focused images) and a tinted plano lens of equal transmittance over the other eye (hyperopic, but potentially clear). After 30, 60, or 240 min, one animal from each group was euthanized, eyes were removed, hemisected, fixed 3 hr in 4% buffered paraformaldehyde, cryosectioned, and labeled by immunofluorescence for Egr-1 or Fos (Fra-2) plus bipolar and amacrine cell markers. Results: (1) Egr-1: After all durations of plus-lens treatment, Egr-1-immunoreactive (IR) bipolar and amacrine cell nuclei were seen, more in the treated than in the control eye; diffusers had the opposite effect (unpaired t-test: P<0.0001). Egr-1-IR was localized to putative cone-ON-bipolars and GABA-ergic and nitroxergic amacrine cells, but not parvalbumin-, calretinin-, calbindin-, cellular retinoic acid binding protein-, or tyosine hydroxylase-IR amacrines; the fraction of GABA-ergic amacrine cells that were Egr-1-IR was higher in plus-lens eyes, and lower in diffuser eyes, than in plano controls. Overall Egr-1 expression was higher in plus-lens retinas and controls contralateral to diffusers (rich in in-focus images) but lower in diffuser retinas and controls contralateral to plus-lenses (images unfocused or hyperopically defocused). (2) Fos: Fra-2-IR was induced only in amacrine cells, and the percent of GABA-IR amacrines labeled for Fra-2 was decreased by diffusers but not affected significantly by plus-lenses. Fra-2 expression was higher in control retinas contralateral to diffusers, and lower in retinas treated otherwise. Conclusions: In infant macaques, hyperopic defocus or form-deprivation causes less activity than unrestricted normal vision in cone-ON-bipolar cells and amacrine cells. Since they respond to defocus, these cells may play a critical role in emmetropization.
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