The theory of visually guided ocular growth is well supported in explaining myopia, but how the retina senses focus versus defocus and converts the signaling into growth-modulating genetic signals remains unresolved. Using whole-cell recordings and single-cell RNA-seq in the mouse retina, we show that lateral inhibitory networks-horizontal cells in the outer retina, but not AII amacrine cells in the inner retina-respond to optical defocus. Dopaminergic amacrine cells (DACs) are maximally excited by focused images and increasingly inhibited by high blur, consistent with dopamine's anti-myopiagenic role. sc-RNA seq revealed stable cell-class composition but coordinated, cell type-specific remodeling of GABAergic synapse and gap junction pathways in lens-induced myopic (LIM) retinas. Consistent with a key role for retinal dopamine signaling, we found gene-level, cell-type-specific remodeling: Atf4 and Gnb5 were significantly upregulated in highly myopic retinas, whereas multiple dopamine pathway components (Gnas, Camk2d, Prkca, Creb1, Plcb4, Drd2, Drd1) were significantly downregulated. Together, our results support a general principle: neuromodulator-gated electrical coupling shapes computations for signal discrimination, and chronic sensory blur in LIM drives cross-level plasticity-from biophysical states to gene expression-that biases downstream coding and growth signals. Targeted manipulation of dopaminergic signaling may restore adaptive defocus encoding and slow myopic progression.
So et al. (Mon,) studied this question.
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