Abstract
Dry eye disease (DED) is a common disorder causing discomfort and ocular fatigue. Corneal nerves are compromised in DED, which may further cause loss of corneal sensation and decreased tear secretion. Semaphorin 3A (Sema3A) is expressed by the corneal epithelium under stress, and is known as an inhibitor of axonal regeneration. Using a murine dry eye model, we found that topical SM-345431, a selective Sema3A inhibitor, preserved corneal sensitivity (2.3 ± 0.3 mm versus 1.4 ± 0.1 mm in vehicle control, p = 0.004) and tear volume (1.1 ± 0.1 mm versus 0.3 ± 0.1 mm in vehicle control, p < 0.001). Fluorescein staining area of the cornea due to damage to barrier function was also reduced (4.1 ± 0.9% in SM-345431 group versus 12.9 ± 2.2% in vehicle control, p < 0.001). The incidence of corneal epithelial erosions was significantly suppressed by SM-345431 (none in SM-345431 group versus six (21%) in vehicle control, p = 0.01). Furthermore, sub-epithelial corneal nerve density and intraepithelial expression of transient receptor potential vanilloid receptor 1 (TRPV1) were significantly preserved with SM-345431. Our results suggest that inhibition of Sema3A may be an effective therapy for DED.
Highlights
The cornea protects the inner structures of the eye from external stimuli with a highly sophisticated defence system
Mice were divided to two groups, Dry eye disease (DED) mice treated with phosphate-buffered saline (PBS) (Vehicle group), and DED mice treated with SM-345431 (0.5 mg/ ml) (SM-345431 group)
Semaphorin 3A (Sema3A) is an extracellular matrix molecule expressed in the cornea, where it is suggested to have a role in epithelial wound healing[20]
Summary
The cornea protects the inner structures of the eye from external stimuli with a highly sophisticated defence system. Dense nerve fibres in the cornea provide quick blink reflexes and lacrimation that play important roles in protecting the eyes. Damage to the corneal afferent neurons in DED patients has been reported to be associated with the disease[7,8,9]. Our group previously reported that the Sema3A inhibitor SM-345431 (vinaxanthone) promotes regeneration of corneal nerves and recovers corneal sensation in a murine keratoplasty model[19]. DED groups were analysed by Student’s t-test, n = 15 mice/group. We hypothesized that inhibiting Sema3A may protect afferent nerves from damage due dry eye. We examined the effect of SM-345431 on corneal epithelial sensation, corneal epithelial barrier function, tear volume and corneal epithelial nerve density in a murine dry eye model
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