Cross-species and cross-platform analysis reveals the application value of guinea pig retina in myopia research at single-cell resolution.

This study delineates the single-cell transcriptomic landscape of pigmented guinea pig retinas-an emerging model for myopia research-through integrated single-cell and bulk RNA sequencing, cross-species comparative analysis, and functional validation using form-deprivation myopia models with intravitreal brimonidine intervention. Our results identified six major retinal cell types (rod cells, cone cells, bipolar cells, Müller glial cells, astrocytes, and retinal pigment epithelial cells) subdivided into 16 distinct subclusters, revealing multilineage pseudo time trajectories and specialized intercellular signaling networks: rod cells via NEGR/CADM, cone cells via MPZ, bipolar cells via SEMA6/PTPRM, and astrocytes via ESAM. Cross-species alignment demonstrated closer phylogenetic alignment with human retinal architecture than murine counterparts in pseudo time trajectories and cellular crosstalk. In therapeutic models, brimonidine treatment decelerated axial elongation while inducing selective reductions in cone cells, bipolar cells, and pigment epithelium, paralleled by concordant gene expression shifts. By establishing the first single cell atlas of guinea pig retina and validating its similarities to human ocular biology, this work not only consolidates guinea pigs as a valuable model for myopia research but also infers cellular and molecular dynamics underlying antimyopic interventions, offering a cross-species framework for retinal disease mechanism exploration and therapeutic development.