The Mouse Retina as an Evolving Model System: From Layered Anatomy to Cell-Type-Resolved Regenerative Repair

The mouse retina has become a central model for linking neural organization to degeneration and repair because it combines laminated anatomy, genetic access, longitudinal imaging, and measurable visual function. This review is organized around three methodological eras: anatomical foundations (1970s-1990s), genetic access and reproducible injury models (2000s-2010s), and cell-resolved omics and high-resolution in vivo imaging (2015-present). Four Method Boxes translate this history into practical guidance for histology, electrophysiology, genetic manipulation, and in vivo imaging. We then examine two therapeutic areas that expose the model's evidentiary limits: retinal ganglion cell (RGC) axon regeneration after optic nerve injury and stage-matched treatment of photoreceptor degeneration. Across both areas, survival, local function, long-distance regeneration, circuit reconnection, and behavior are treated as distinct outcomes. The mouse retina is therefore most informative when complementary readouts are combined and promising mechanisms are tested against human-relevant tissue and larger-eye systems before clinical inference.