Abstract |
Dry eye disease (DED) is a common disorder causing discomfort and ocular fatigue. Corneal nerves are compromised in DED, which may further cause loss of corneal sensation and decreased tear secretion. Semaphorin 3A ( Sema3A) is expressed by the corneal epithelium under stress, and is known as an inhibitor of axonal regeneration. Using a murine dry eye model, we found that topical SM-345431, a selective Sema3A inhibitor, preserved corneal sensitivity (2.3 ± 0.3 mm versus 1.4 ± 0.1 mm in vehicle control, p = 0.004) and tear volume (1.1 ± 0.1 mm versus 0.3 ± 0.1 mm in vehicle control, p < 0.001). Fluorescein staining area of the cornea due to damage to barrier function was also reduced (4.1 ± 0.9% in SM-345431 group versus 12.9 ± 2.2% in vehicle control, p < 0.001). The incidence of corneal epithelial erosions was significantly suppressed by SM-345431 (none in SM-345431 group versus six (21%) in vehicle control, p = 0.01). Furthermore, sub-epithelial corneal nerve density and intraepithelial expression of transient receptor potential vanilloid receptor 1 (TRPV1) were significantly preserved with SM-345431. Our results suggest that inhibition of Sema3A may be an effective therapy for DED.
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Authors | Risa Yamazaki, Katsuya Yamazoe, Satoru Yoshida, Shin Hatou, Emi Inagaki, Hideyuki Okano, Kazuo Tsubota, Shigeto Shimmura |
Journal | Scientific reports
(Sci Rep)
Vol. 7
Issue 1
Pg. 15584
(11 14 2017)
ISSN: 2045-2322 [Electronic] England |
PMID | 29138447
(Publication Type: Journal Article)
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Chemical References |
- Semaphorin-3A
- TRPV Cation Channels
- TRPV1 protein, mouse
- Xanthones
- vinaxanthone
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Topics |
- Animals
- Cornea
(drug effects, innervation, pathology)
- Corneal Injuries
(drug therapy, genetics, pathology)
- Disease Models, Animal
- Dry Eye Syndromes
(drug therapy, genetics, pathology)
- Epithelium, Corneal
(drug effects, metabolism, pathology)
- Gene Expression Regulation
(drug effects)
- Humans
- Mice
- Semaphorin-3A
(antagonists & inhibitors, genetics)
- TRPV Cation Channels
(genetics)
- Tears
(drug effects)
- Xanthones
(administration & dosage)
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