2021 Fiscal Year Final Research Report
Pathophysiology of neurogenic olfactory dysfunction
| Project/Area Number |
18KK0448
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2018 – 2021
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| Keywords | 嗅粘膜 / 蛍光プローブ / 嗅覚障害 |
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| Outline of Final Research Achievements |
Olfactory epithelium (OE) undergoes degeneration in disorders such as age-related olfactory dysfunction. However, methods for real-time in vivo detection of OE and assessment of total extent in the nasal cavity are unavailable. We identified two fluorescence probes for rapidly detecting and evaluating the entire extent of mice OE with topical application. Taking advantage of the differential expression of the enzymes cytochrome p450(CYP) and γ-glutamyltranspeptidase(GGT) in OE relative to respiratory epithelium, we utilized the conversion of coumarin(a substrate of CYP) and gGlu-HRMG(a substrate of GGT) by these enzymes to form metabolites with fluorescent emissions in the duct and sustentacular cells of neuron-containing OE. In depleted and regenerated OE model, the emission of these probes remained absent in respiratory metaplasia but appeared in regenerated OE. These substrates could be used to monitor OE degeneration and follow regenerative response to therapeutic interventions.
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| Free Research Field |
鼻科学
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| Academic Significance and Societal Importance of the Research Achievements |
これらのプローブが将来的にヒトでの応用が可能となった場合、内視鏡下の観察により嗅粘膜の状態を観察できるようになる。このことは嗅覚障害の疾患分類そのものを変え、嗅覚診療の大きな変換点となる可能性がある。さらにこの嗅粘膜特異的プローブにより嗅粘膜を直接可視化できるようになることは、耳鼻咽喉科診療で行われている内視鏡下鼻副鼻腔手術や頭蓋底手術等での有用性も期待される。
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