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William K. Stell, Jin Tao, Artee Karkhanis, John T. Siegwart, Thomas T. Norton; Intensity- and focus-dependent modulation of activity (expression of immediate-early gene products) in retinal interneurons of the tree shrew, tupaia glis belangeri6o. Journal of Vision 2003;3(12):53. doi: https://doi.org/10.1167/3.12.53.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Retinal visual processing of visual stimuli and locally acting signaling mechanisms play critical roles in ocular growth-regulation and emmetropization. Putative amacrine cell mediators of emmetropization have been identified in chicks by visual induction of transcription factors Egr1 and Fra2. Here we report results of similar studies in a mammalian model of emmetropization.
Methods: 21 days after eyelid opening, 8 tree shrews were fitted with a lens-holder. 3 days later one eye was covered with a diffuser (form-deprived). After 11 days, when the deprived eye was ∼5.5–8.5 D myopic, the diffuser was replaced with a plano lens, either untinted (“intensity-increase”, N=4) or tinted to equal the 30% absorption of the diffuser (“isoluminant exchange”, N=4), and unrestricted vision was allowed for 1–3 hr. Eyes were perfused with paraformaldehyde, cryosections were immunolabeled for Egr1 or Fra2 plus amacrine cell markers, and labeling by Egr1 or Fra2 was quantified.
Results: (1) Intensity-increase stimulated Fra2 and Egr1 in amacrine cells (e.g., Fra2 amacrines/area: 17.2+1.6 treated vs 14.2 +2.2 control, P=0.03; Egr1 amacrines/area: 4.7+1.0 vs 1.1+0.5, P=0.02; N=4 animals). Fra2 was induced in GAD65 and PKC/Gly amacrines, and Egr1 in CaMKII amacrine s, among others. (2) In isoluminant exchange, more activity (% amacrines labeled) was detected in control than in treated retinas, particularly Egr1 in PKC/Gly amacrines (control vs treated: 61.9+8.0, vs 33.9+6.0, P=0.02, and 52.6+6.0 vs 14.3+3.5; P<0.0001; N=20 fields).
Conclusions: Intensity-increase induced Egr1 and Fra2 in amacrine cells in myopic eyes. PKC/Gly amacrine cells were either inhibited in myopic eyes, or stimulated in control eyes, and therefore could participate in defocus-compensation.
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