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Semaphorin 7a links nerve regeneration and inflammation in the cornea.

AbstractPURPOSE:
We determined Semaphorin 7a (Sema7a) localization and abundance in naive corneas and in corneas after nerve-transecting lamellar flap surgery, and determined the effect of Sema7a supplementation on corneal nerve regeneration and inflammation.
METHODS:
Immunolocalization and Western blot analyses were performed to evaluate the abundance of Sema7a in naive corneas and corneas undergoing nerve regeneration after lamellar corneal surgery in thy1-YFP+ neurofluorescent mice. We used compartmental cultures of dissociated trigeminal ganglion cells to determine the effect of Sema7a exposure on neurite outgrowth in vitro. Finally, a Sema7a pellet was implanted under the corneal flap after lamellar transection surgery to determine the neuronal and inflammatory effects of Sema7a supplementation in vivo.
RESULTS:
Sema7a was expressed in the corneal epithelium and stromal keratocytes, but was more abundant in the epithelium (74.3%) compared to the stroma (25.7%, P = 0.02). Sema7a expression was increased significantly in the cornea after lamellar corneal surgery and was localized to stromal cells near the regenerating nerve fronds. Exposure of trigeminal neurites to Sema7a (20 nM) in the side compartment increased neurite length significantly. The implanted Sema7a pellet increased significantly YFP+ inflammatory cell influx into the cornea as well as increased corneal nerve length.
CONCLUSIONS:
Sema7a is expressed constitutively in the cornea, and potently stimulates nerve regeneration and inflammatory cell influx. Therefore, this immune semaphorin links nerve regeneration and inflammatory processes in the cornea.
AuthorsAbed Namavari, Shweta Chaudhary, Okan Ozturk, Jin-Hong Chang, Lisette Yco, Snehal Sonawane, Neelima Katam, Vishakha Khanolkar, Joelle Hallak, Joy Sarkar, Sandeep Jain
JournalInvestigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 53 Issue 8 Pg. 4575-85 (Jul 09 2012) ISSN: 1552-5783 [Electronic] United States
PMID22700709 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD
  • Sema7a protein, mouse
  • Semaphorins
  • DNA
Topics
  • Animals
  • Antigens, CD (biosynthesis, genetics)
  • Blotting, Western
  • Cells, Cultured
  • Cornea (innervation, metabolism, pathology)
  • DNA (genetics)
  • Disease Models, Animal
  • Gene Expression Regulation
  • Keratitis (genetics, metabolism, pathology)
  • Mice
  • Microscopy, Confocal
  • Nerve Regeneration
  • Real-Time Polymerase Chain Reaction
  • Semaphorins (biosynthesis, genetics)

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