Semaphorin 7a links nerve regeneration and inflammation in the cornea.
OBJECTIVE
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.
Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, 60612, USA.
Abed
A
Namavari
Shweta
S
Chaudhary
Okan
O
Ozturk
Jin-Hong
JH
Chang
Lisette
L
Yco
Snehal
S
Sonawane
Neelima
N
Katam
Vishakha
V
Khanolkar
Joelle
J
Hallak
Joy
J
Sarkar
Sandeep
S
Jain
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D015153:Blotting, Western; D002478:Cells, Cultured; D003315:Cornea / Q000294:innervation* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007634:Keratitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018613:Microscopy, Confocal; D009416:Nerve Regeneration; D060888:Real-Time Polymerase Chain Reaction; D039961:Semaphorins / Q000096:biosynthesis / Q000235:genetics*
D015703:Antigens, CD; C485571:Sema7a protein, mouse; D039961:Semaphorins; D004247:DNA