Fig. 8: Schematic illustration of the cochlin/SFRP1/CaMKII axis identified in this study.

The blurred visual image in the retina induced dramatic upregulation of cochlin (red dots), an ECM protein, at the interface between retinal photoreceptor cells and RPE cells. Cochlin protein stimulated RPE cells to enhance the production and secretion of SFRP1 (orange dots), which in turn acted upon the endothelial cells of ChC and ChV and caused endothelial cell dysfunction, including boosted apoptosis, diminished aggregation, and augmented migration, through activation of the noncanonical Wnt/Ca²⁺/CaMKII signaling pathway. Endothelial cell dysfunctions may elicit reduced vessel lumen area and waned blood perfusion in the choroid, eventually leading to nonpathologic myopia. Targeting cochlin and SFRP1 on the axis precluded the progression of nonpathologic myopia by improving choroidal circulation. RPE retinal pigment epithelium, SFRP1 secreted frizzled-related protein 1, ONL outer nuclear layer, IS inner segments, OS outer segments, ChC choriocapillaris, ChV choroidal vessels, p-CaMKII phosphorylated Ca²⁺/calmodulin-dependent protein kinase II.