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Karger AG","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells Tissues Organs"],"abstract":"<jats:p>Background: Chronic aqueous-deficient dry eye is usually attributed to lacrimal gland and ocular surface pathology, whereas the parasympathetic structures controlling tear secretion receive little attention in this context. The pterygopalatine ganglion (PPG) relays parasympathetic (secretomotor) fibres to the lacrimal gland (as well as to the nasal, palatal, and conjunctival glands) and it contributes to cerebrovascular vasodilatation. However, whether PPG injury contributes to secretory dysfunction, particularly in diabetes mellitus, remains insufficiently studied. Summary: We reviewed evidence from ocular surface disease, autonomic neuropathy, diabetes-related neuronal injury, regulated cell death, surgical denervation, and cerebrovascular physiology and found that interruption of the PPG pathway indeed reduces lacrimal secretion and produces aqueous-deficient dry eye. In streptozotocin-induced diabetic rats, nitrergic PPG neurons undergo TUNEL-positive apoptosis during the irreversible phase of nitrergic neuropathy. The experimental data implicates advanced glycation end products, their receptor RAGE, endogenous nitric oxide, and caspase-3 activation. Necroptosis, pyroptosis, ferroptosis, and satellite glial injury are plausible specific causes but have not been demonstrated directly to occur in PPG injury. On the basis of additional evidence, we hypothesize that impaired nasal mucociliary clearance, reduced palatal secretion, conjunctival goblet-cell abnormalities, and altered cerebrovascular regulation may arise from the same ganglionic lesion. Key Messages: Diabetic apoptosis of nitrergic PPG neurons is experimentally established in rodents and may represent an upstream mechanism of the dry eye syndrome. Our hypothesis of a diabetic secretory denervation syndrome may be tested by targeted histological, functional, and clinical investigation. Such studies may also clarify whether PPG neuroprotection has therapeutic value.<\/jats:p>","DOI":"10.1159\/cto\/acbag003","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T11:32:37Z","timestamp":1787052757000},"page":"1-1","source":"Crossref","is-referenced-by-count":0,"title":["Pterygopalatine Ganglion Cell Death as an Under-Recognized Mechanism in Dry Eye Syndrome: A Hypothesis with Special Attention to Diabetic Aetiology"],"prefix":"10.1159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8723-0540","authenticated-orcid":false,"given":"Mugurel Constantin","family":"Rusu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Alexandra","family":"B\u0103nic\u0103","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra 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