Document Detail

Cyclosporine immunomodulation retards regeneration of surgically transected corneal nerves.
MedLine Citation:
PMID:  22205605     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To determine whether immunomodulation with cyclosporine (CsA) affects reinnervation after surgical transection of stromal nerves.
METHODS: Thy1-YFP+ neurofluorescent mice underwent lamellar corneal surgery and 3 days later, received artificial tears or CsA eye drops for 6 weeks. Serial in vivo wide-field stereofluorescent microscopy was performed to determine changes in nerve fiber density (NFD). Real-time quantitative PCR was performed to determine the expression of neurotrophins and cytokines (IL6 and TNF-α). Compartmental culture of trigeminal ganglion neurons was performed in Campenot devices to determine whether CsA directly affects neurite outgrowth.
RESULTS: Yellow fluorescent protein (YFP)-positive cells significantly increased at 3 and 7 days after surgery. The number of YFP-positive cells in the cornea was significantly lower in the CsA group than that in the control group. The percentage increase in NFD between 2 to 6 weeks was greater in the control group (80% ± 10%, P = 0.05) than that in the CsA group (39% ± 21%). The CsA group also exhibited lower expression of IL6 and TNF-α (P = 0.01). In compartmental culture experiments, neurite outgrowth toward side compartments containing CsA was significantly less (2.29 ± 0.4 mm, P = 0.01) than that toward side compartments containing vehicle (3.97 ± 0.71 mm).
CONCLUSIONS: Immunomodulation with CsA reduces the expression of cytokines (IL6) in the cornea and retards regenerative sprouting from transected corneal stromal nerve trunks. In addition, CsA has a direct growth inhibitory action on neurites as well.
Abed Namavari; Shweta Chaudhary; Jin-Hong Chang; Lisette Yco; Snehal Sonawane; Vishakha Khanolkar; Beatrice Y Yue; Joy Sarkar; Sandeep Jain
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-13
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  53     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-14     Completed Date:  2012-04-03     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  732-40     Citation Subset:  IM    
Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois 60612, USA.
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MeSH Terms
Cornea / innervation*,  physiology*,  surgery
Corneal Stroma / innervation
Cyclosporine / pharmacology*
Immunosuppressive Agents / pharmacology*
Interleukin-6 / metabolism
Nerve Growth Factors / metabolism
Neurites / metabolism
Real-Time Polymerase Chain Reaction
Regeneration / drug effects*
Tumor Necrosis Factor-alpha / metabolism
Grant Support
EY001792/EY/NEI NIH HHS; EY018874/EY/NEI NIH HHS; K08 EY018874/EY/NEI NIH HHS; P30 EY001792-34/EY/NEI NIH HHS; R21 EY021886/EY/NEI NIH HHS
Reg. No./Substance:
0/Immunosuppressive Agents; 0/Interleukin-6; 0/Nerve Growth Factors; 0/Tumor Necrosis Factor-alpha; 59865-13-3/Cyclosporine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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