{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T12:37:40Z","timestamp":1780922260365,"version":"3.54.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Glaucoma, the leading cause of irreversible blindness worldwide, is characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons. While elevated intraocular pressure (IOP) is a core risk factor, the pathogenesis of normal-tension glaucoma (NTG) remains unclear, as static IOP is within the normal range. Based on circadian fluctuations of IOP and cerebrospinal fluid pressure (CSFP), and the pressure-dependent function of the ocular glymphatic system, we propose the \u201cdynamic trans-lamina cribrosa pressure difference (TLCPD) imbalance\u201d hypothesis. This hypothesis posits that optic nerve damage may stem from abnormal pulse synchrony between IOP and CSFP (phase mismatch, amplitude mismatch, or abnormal frequency) rather than static TLCPD elevation alone, pending further validation. Dynamic imbalance induces RGC injury through dual mechanisms: mechanical stress on the lamina cribrosa (collagen fiber rupture, astrocyte activation) and metabolic dysfunction (ocular glymphatic clearance impairment, toxic waste accumulation), which ultimately converge on the activation of the programmed axonal degeneration (PAD) pathway\u2014a conserved final common effector of RGC axon loss. Phase mismatch is the core pathological pattern in NTG. In contrast, high-tension primary open-angle glaucoma (POAG) is characterized mainly by amplitude mismatch and abnormal frequency, with potential coexistence and mutual influence of these mechanisms. Verifiable clinical (24-h IOP-CSFP synchronous monitoring) and animal experiments are proposed. This hypothesis may help explain unresolved clinical phenomena, provides novel diagnostic markers (a transient peak in TLCPD) and therapeutic strategies (CSFP regulation, glymphatic function enhancement, modulation of the PAD pathway), and opens new avenues for personalized glaucoma management.<\/jats:p>","DOI":"10.3389\/fmed.2026.1781347","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:25:30Z","timestamp":1774329930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Pulsed synchrony regulation of intraocular and cerebrospinal fluid pressure: a novel paradigm for glaucoma pathogenesis and treatment"],"prefix":"10.3389","volume":"13","author":[{"given":"Bin","family":"Lin","sequence":"first","affiliation":[{"name":"Xiamen Eye Center and Eye Institute of Xiamen University, School of Medicine","place":["Xiamen, China"]},{"name":"Xiamen Clinical Research Center for Eye 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Key Laboratory of Corneal & Ocular Surface Diseases","place":["Xiamen, Fujian, China"]},{"name":"Translational Medicine Institute of Xiamen Eye Center of Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Ting","family":"Li","sequence":"additional","affiliation":[{"name":"Xiamen Eye Center and Eye Institute of Xiamen University, School of Medicine","place":["Xiamen, China"]},{"name":"Xiamen Clinical Research Center for Eye Diseases","place":["Xiamen, Fujian, China"]},{"name":"Xiamen Key Laboratory of Ophthalmology","place":["Xiamen, Fujian, China"]},{"name":"Fujian Key Laboratory of Corneal & Ocular Surface Diseases","place":["Xiamen, Fujian, China"]},{"name":"Xiamen Key Laboratory of Corneal & Ocular Surface Diseases","place":["Xiamen, Fujian, China"]},{"name":"Translational Medicine Institute of Xiamen Eye Center of Xiamen University","place":["Xiamen, Fujian, 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