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Background: Fungal keratitis (FK) is eye microbial infection disease which can leads to severe corneal blindness. Corneal scar formation is one of the major complications of fungal keratitis and is closely related to prognosis. The aim of the current investigation was to evaluate the anti-fibrosis effect of human umbilical cord mesenchymal stem cells (uMSCs) in FK model and further to explore underlying mechanisms.
Methods: FK mice model was made by corneal epithelial scratching and F. solani inoculation. The C57BL/6J mice were randomly divided into four groups, including control group, FK group, vehicleinj FK group and uMSCsinj FK group. After injury, antifungal drug natamycin eye drops were used topically to FK mice eyes 6 times per day for 7 days to inhibit fungi growth. Mice received repeated subconjunctival injection of uMSCs or veichle for 3 times including the 1d, 4d and 7d after wounding. At 14d, 21d and 28d post-injury, clinical observation, histological examination, second harmonic generation, immunofluoresence staining and molecular assays were performed.
Results: The uMSCs topical administration reduced corneal scar formation and corneal opacity, accompanying with decreased corneal thickness and inflammatory cell infiltration, following down-regulated fibrotic-related factors α-SMA, TGFβ1, CTGF, and COLⅠ and finally inhibited phosphorylation of TGFβ1/Smad2 signaling pathway, which indicating the potential anti-fibrotic and protective effect of human uMSCs against FK-induced corneal fibrosis.
Conclusion: Human uMSCs can evidently inhibit corneal fibrosis after FK wounding through TGFβ1/Smad2 signaling pathway regulation.
Keywords: Fungal keratitis, corneal fibrosis, umbilical cord mesenchymal stem cells
Keywords
Fungal keratitis, corneal fibrosis, umbilical cord mesenchymal stem cells
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CURRENT STATUS: Published
View the published article at BMC Ophthalmology.
No community comments so far
Editorial decision: Minor revision
On 25 Oct, 2019
Review #1 received
Received 23 Aug, 2019
Editor assigned
On 31 Jul, 2019
Reviewers invited
Invitations sent on 31 Jul, 2019
Reviewer #1 agreed
On 31 Jul, 2019
Submission checks complete
On 30 Jul, 2019
Editor invited
On 30 Jul, 2019
No comments provided
Editorial decision: Major revision
On 15 Jul, 2019
Review #2 received
Received 09 Jul, 2019
Review #1 received
Received 27 Jun, 2019
Reviewer #1 agreed
On 25 Jun, 2019
Reviewer #2 agreed
On 25 Jun, 2019
Reviewers invited
Invitations sent on 25 Jun, 2019
Submission checks complete
On 20 Jun, 2019
Editor invited
On 20 Jun, 2019
Editor assigned
On 20 Jun, 2019
Version 1
Posted 09 Jan, 2019
No comments provided
Editorial decision: Major revision
On 30 May, 2019
Review #2 received
Received 22 May, 2019
Reviewer #2 agreed
On 13 May, 2019
Review #1 received
Received 14 Mar, 2019
Reviewers invited
Invitations sent on 18 Feb, 2019
Reviewer #1 agreed
On 18 Feb, 2019
Submission checks complete
On 08 Jan, 2019
Editor invited
On 08 Jan, 2019
Editor assigned
On 04 Jan, 2019
First submitted
On 27 Dec, 2018
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A new preprint design is coming!
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See the published version of this preprint at BMC Ophthalmology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Ophthalmology.
No community comments so far
Editorial decision: Minor revision
On 25 Oct, 2019
Review #1 received
Received 23 Aug, 2019
Editor assigned
On 31 Jul, 2019
Reviewers invited
Invitations sent on 31 Jul, 2019
Reviewer #1 agreed
On 31 Jul, 2019
Submission checks complete
On 30 Jul, 2019
Editor invited
On 30 Jul, 2019
No comments provided
Editorial decision: Major revision
On 15 Jul, 2019
Review #2 received
Received 09 Jul, 2019
Review #1 received
Received 27 Jun, 2019
Reviewer #1 agreed
On 25 Jun, 2019
Reviewer #2 agreed
On 25 Jun, 2019
Reviewers invited
Invitations sent on 25 Jun, 2019
Submission checks complete
On 20 Jun, 2019
Editor invited
On 20 Jun, 2019
Editor assigned
On 20 Jun, 2019
Version 1
Posted 09 Jan, 2019
No comments provided
Editorial decision: Major revision
On 30 May, 2019
Review #2 received
Received 22 May, 2019
Reviewer #2 agreed
On 13 May, 2019
Review #1 received
Received 14 Mar, 2019
Reviewers invited
Invitations sent on 18 Feb, 2019
Reviewer #1 agreed
On 18 Feb, 2019
Submission checks complete
On 08 Jan, 2019
Editor invited
On 08 Jan, 2019
Editor assigned
On 04 Jan, 2019
First submitted
On 27 Dec, 2018
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Internal Medicine Specialties
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Ophthalmology.
Background: Fungal keratitis (FK) is eye microbial infection disease which can leads to severe corneal blindness. Corneal scar formation is one of the major complications of fungal keratitis and is closely related to prognosis. The aim of the current investigation was to evaluate the anti-fibrosis effect of human umbilical cord mesenchymal stem cells (uMSCs) in FK model and further to explore underlying mechanisms.
Methods: FK mice model was made by corneal epithelial scratching and F. solani inoculation. The C57BL/6J mice were randomly divided into four groups, including control group, FK group, vehicleinj FK group and uMSCsinj FK group. After injury, antifungal drug natamycin eye drops were used topically to FK mice eyes 6 times per day for 7 days to inhibit fungi growth. Mice received repeated subconjunctival injection of uMSCs or veichle for 3 times including the 1d, 4d and 7d after wounding. At 14d, 21d and 28d post-injury, clinical observation, histological examination, second harmonic generation, immunofluoresence staining and molecular assays were performed.
Results: The uMSCs topical administration reduced corneal scar formation and corneal opacity, accompanying with decreased corneal thickness and inflammatory cell infiltration, following down-regulated fibrotic-related factors α-SMA, TGFβ1, CTGF, and COLⅠ and finally inhibited phosphorylation of TGFβ1/Smad2 signaling pathway, which indicating the potential anti-fibrotic and protective effect of human uMSCs against FK-induced corneal fibrosis.
Conclusion: Human uMSCs can evidently inhibit corneal fibrosis after FK wounding through TGFβ1/Smad2 signaling pathway regulation.
Keywords: Fungal keratitis, corneal fibrosis, umbilical cord mesenchymal stem cells
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
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