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. Author manuscript; available in PMC: 2015 May 1.
Published in final edited form as: Surv Ophthalmol. 2014 Jan 23;59(3):263–285. doi: 10.1016/j.survophthal.2013.09.002

TABLE 4.

Modulators that affect neuronal as well as inflammatory pathways

Factor Effect on corneal nerves Effect on inflammation
Biological factors
NGF Nerve regeneration 66 Pro 36,120,129
VEGF Efficient regeneration 127 Pro 99
DHA Enhances regeneration 66 Anti 49
PACAP Neurite outgrowth
Accelerates return of corneal sensitivity after injury 76 		Pro 224
Slit2 Axonal repulsion (early development) 113
Epithelial nerve branching (late development) 113 		Anti 213
Sema7A Axonal elongation
Neurite outgrowth
Nerve regeneration 164 		Pro 164
T lymphocytes Enhances regeneration 127 Pro 127
LIF Accelerates regeneration 177 Pro or anti 189
IL-17 Enhances regeneration 127 Pro 127
Pharmacologic factors
Cyclosporine A Mixed:
Improved indirect measures of corneal nerve function58*
Retards regeneration 163 		Anti 58,163
Corticosteroids Mixed:
May reverse neuropathic morphologies 117
Improvement or no change in indirect corneal nerve function tests121* 		Anti 121,125
Opioids Corneal reflex blockade 218
Analgesia 187 		Anti 222†
Benzalkonium chloride Neurotoxicity 197 Pro 197

NGF= nerve growth factor; VEGF = vascular endothelial growth factor; DHA = docosahexanoic acid; PACAP = pituitary adenylate cyclase-activating peptide; Sema7A = semaphorin 7A; LIF = leukemia inhibitory factor; IL-17 = interleukin 17. “ – ” = no known effect.

*

In these publications, corneal nerve function was measured indirectly by tests that assess elements of the nerve-epithelium-tear film axis, (such as Schirmer’s, tear film breakup time, and/or fluorescent dyes for epithelial integrity), as well as subjective symptoms (such as dry eye and foreign body sensation).

†

Evidence supports the anti-inflammatory properties of kappa opioids, while the effect of other opioid classes on inflammation remains unclear.