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Published on: December 8, 2023
Cyclosporine immunomodulation retards regeneration of surgically transected corneal nerves
Abed Namavari1, Shweta Chaudhary, Jin-Hong Chang
1Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois 60612, USA.
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.
Insights
Cyclosporine (CsA) eye drops reduce corneal nerve regeneration after surgery by inhibiting cytokine expression and directly impairing neurite outgrowth. This immunomodulation impacts nerve fiber density recovery.
Area of Science:
- Ophthalmology
- Neuroscience
- Immunology
Background:
- Corneal nerve damage can impair vision and sensation.
- Understanding factors influencing nerve regeneration is crucial for effective treatment.
- Immunomodulatory drugs may impact neural healing processes.
Purpose of the Study:
- To investigate the effect of cyclosporine (CsA) on corneal nerve reinnervation following surgical injury.
- To determine if CsA influences the expression of key neurotrophic and inflammatory factors.
- To assess the direct impact of CsA on neuronal growth in vitro.
Main Methods:
- Lamellar corneal surgery was performed on Thy1-YFP+ mice, followed by treatment with artificial tears or CsA eye drops.
- In vivo microscopy tracked changes in nerve fiber density (NFD).
- Quantitative PCR analyzed cytokine expression (IL6, TNF-α), and compartmental cultures assessed CsA's effect on neurite outgrowth.
Main Results:
- CsA treatment led to a significantly lower increase in corneal nerve fiber density compared to controls.
- Expression of IL6 and TNF-α was reduced in the CsA group.
- In vitro, CsA directly inhibited neurite outgrowth from trigeminal ganglion neurons.
Conclusions:
- Cyclosporine (CsA) impairs corneal nerve regeneration after surgical transection.
- CsA reduces pro-inflammatory cytokine expression in the cornea.
- CsA exhibits a direct inhibitory effect on neuronal growth, hindering nerve repair.
