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Defocus coding and transcriptomic remodeling in the mouse myopic retina
ChungHim So1, Ting Zhang1, Kangyi Yang1,2
1School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong, People's Republic of China.
American Journal of Physiology. Cell Physiology
|March 30, 2026
Summary
The retina detects optical defocus via horizontal cells, influencing dopaminergic amacrine cells (DACs). This process, involving gene expression changes in lens-induced myopic (LIM) retinas, suggests targeting dopamine signaling could slow myopia progression.
Area of Science:
- Neuroscience
- Ophthalmology
- Genetics
Background:
- Myopia development is linked to visually guided ocular growth.
- The precise retinal mechanisms for sensing focus/defocus and translating them into growth signals are unclear.
Purpose of the Study:
- Investigate how retinal circuits and gene expression respond to optical defocus.
- Determine the role of retinal dopamine signaling in myopia progression.
Main Methods:
- Whole-cell recordings and single-cell RNA sequencing (sc-RNA-seq) in mouse retinas.
- Analysis of retinas from lens-induced myopic (LIM) mice.
Main Results:
- Horizontal cells, not AII amacrine cells, respond to optical defocus.
- Dopaminergic amacrine cells (DACs) show altered activity with defocus, consistent with dopamine's anti-myopiagenic role.
- sc-RNA-seq revealed cell-type-specific remodeling of synaptic pathways and altered gene expression (e.g., Atf4, Gnb5 upregulation; dopamine pathway downregulation) in LIM retinas.
Conclusions:
- Neuromodulator-gated electrical coupling influences signal discrimination.
- Chronic blur in LIM retinas induces plasticity from biophysical states to gene expression, impacting growth signals.
- Targeting dopaminergic signaling may offer a strategy to slow myopia progression by restoring adaptive defocus encoding.
