From mechanotransduction to manual therapy: advances in piezo/TRP channels and lumbar degeneration.

Myopia has emerged as a major global public health challenge, while pathological myopia representing a leading cause of irreversible visual impairment worldwide (), affecting 3% of the global population () and 12–27% of Asian populations (; ; ). Beyond refractive error, pathological myopia is characterized by excessive axial elongation of the eyeball accompanied by progressive retinal thinning, retinal and choroidal vascular degeneration, and neuronal dysfunction (). These changes culminate in myopic retinopathy, a degenerative condition that shares features with other chronic neurodegenerative diseases but the cellular mechanisms remain poorly understood. Clinically, myopic retinopathy is marked by macular atrophy, lacquer cracks, Fuchs spots, patchy chorioretinal atrophy or choroidal neovascularization (mCNV), and myopic traction maculopathy (; ), and increasing susceptible to secondary complications such as macular degeneration and glaucoma (; ). Although retinal thinning and reduced neuronal density are well documented in highly myopic eyes, it remains unclear whether neuronal changes primarily reflect passive tissue stretching over an enlarged retinal surface or active, cell type–specific neurodegeneration. Dissecting these possibilities is essential for understanding vision loss in myopia and for developing effective neuroprotective strategies for myopia. The retinal pigment epithelium (RPE) plays a central role in maintaining retinal homeostasis by supporting photoreceptor metabolism, regulating ion and fluid transport, controlling immune privilege (; ; ), and mediating bidirectional signaling between the retina and choroid. Disruption of RPE function has been implicated in both retinal degeneration and abnormal eye growth (; ). Low-density lipoprotein receptor–related protein 2 (LRP2, also known as megalin) is a multifunctional endocytic receptor highly expressed in the RPE (), where it regulates the uptake and signaling of multiple ligands, including morphogens and growth factors involved in ocular development (; ). LRP2 mutation is linked to Donnai-Barrow Syndrome, including craniofacial anomalies, sensorineural hearing loss, renal tubular dysfunction, and distinctive ocular features. Mice with Lrp2 deficiency develop enlarged eyeballs and retinal abnormalities (, ; ), offering the opportunity to investigate the cellular mechanisms of myopic retinal degeneration.