One in the eye for eye disease

An experimental drug derived from cobra venom protects the mouse cornea from harmful inflammation by blocking an immune system protein.
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Image credit: Jordan Whitfield (CC0)

Most people have likely experienced the discomfort of an eyelash falling onto the surface of their eye. Or that gritty sensation when dust blows into the eye and irritates the surface. These sensations are warnings from sensory nerves in the cornea, the transparent tissue that covers the iris and pupil. Corneal nerves help regulate blinking, and control production of the tear fluid that protects and lubricates the eye.

But if the cornea suffers damage or infection, it can become inflamed. Long-lasting inflammation can damage the corneal nerves, leading to pain and vision loss. If scientists can identify how this happens, they may ultimately be able to prevent it. To this end, Royer et al. have used mice to study three causes of hard-to-treat corneal inflammation. The first is infection with herpes simplex virus (HSV-1), which also causes cold sores. The second is eye allergy, where the immune system overreacts to substances like pollen or pet dander. And the third is graft-versus-host disease (GVHD), an immune disorder that can affect people who receive a bone marrow transplant.

Royer et al. showed that HSV-1 infection and GVHD – but not allergies – made the mouse cornea less sensitive to touch. Consistent with this, microscopy revealed damage to corneal nerves in the mice with HSV-1 infection and those with GVHD. Further experiments showed that immune cells called CD4 T cells and a protein called complement C3 were contributing to this nerve damage. Treating the mice with an experimental drug derived from cobra venom protected the cornea from the harmful effects of inflammation. It did so by blocking activation of complement C3 at the eye surface.

Identifying factors such as complement C3 that are responsible for corneal nerve damage is an important first step in helping patients with inflammatory eye diseases. Many drugs that target the complement pathway are currently under development. Some of these drugs could potentially be adapted for delivery as eye drops. But first, experiments must test whether complement also contributes to corneal nerve damage in humans. If it does, work can then begin on testing these drugs for safety and efficacy in patients.