TY - JOUR
T1 - The Semaphorin 3A inhibitor SM-345431 preserves corneal nerve and epithelial integrity in a murine dry eye model
AU - Yamazaki, Risa
AU - Yamazoe, Katsuya
AU - Yoshida, Satoru
AU - Hatou, Shin
AU - Inagaki, Emi
AU - Okano, Hideyuki
AU - Tsubota, Kazuo
AU - Shimmura, Shigeto
N1 - Funding Information:
Competing Interests: This work was supported by JSPS KAKENHI Grant number 16K11299 and by a grant from Sumitomo Dainippon Pharma Co Ltd. Funders were not involved with any part of the study design or interpretation of the data.
Funding Information:
?Department of Ophthalmology, Keio university school of medicine, Tokyo, Japan. ?Department of Physiology, Keio university school of medicine, Tokyo, Japan. ?Centre for Rare Disease Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan. Correspondence and requests for materials should be addressed to S.S. (email: ?hige 㬀鰃縁?e)io.jp
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41598-017-15682-1
DO - 10.1038/s41598-017-15682-1
M3 - Article
C2 - 29138447
AN - SCOPUS:85034103919
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 15584
ER -