A protein called nerve growth factor (NGF) — which can block eye inflammation caused by infection with the herpes simplex virus — could have therapeutic applications in herpes simplex keratitis (HSK), a type of neurotrophic keratitis, a study has found.

The study, “Nerve growth factor inhibits TLR3-induced inflammatory cascades in human corneal epithelial cells,” was published in the Journal of Inflammation.

HSK, a form of keratitis caused by infection with herpes simplex virus 1 (HSV-1), can cause damage to the eye and result in blindness. In the cornea (the outermost layer of the eye), cells called corneal epithelial cells play an important role in identifying infectious threats. They do this by using a type of protein that sits on the cell surface called Toll-like receptors (particularly TLR3), which respond to molecular patterns associated with invaders such as viruses and send signals to other cells to evoke an inflammatory response.

However, although the inflammatory response is required to clear the virus, it can also lead to tissue damage and scarring, and potential vision impairment. Understanding the precise molecular mechanisms that govern TLR3-mediated immunity in the eye may open avenues for new therapeutic approaches, researchers say.

The new study focused on the role of NGF in TLR3-mediated immunity. As its name suggests, NGF can help spur the growth of cells in the nervous system, and has a number of other roles in the body, including regulating the immune system. However, the role of NGF in corneal immunity isn’t well-understood.

In the study, researchers treated human corneal epithelial cells (HCECs) grown in the lab with an activator of TLR3 (mimicking what a viral infection would do) in the presence or absence of NGF at various concentrations.

Activation of TLR3 significantly reduced cell viability (compared to cells without such activation). However, treatment with NGF reduced this effect in a dose-dependent manner, with significantly more cells surviving, as compared to cells that had TLR3 activated but weren’t treated with NGF.

Further investigation revealed that TLR3 activation caused activation of another protein, the transcription factor NF-κB. When activated, NF-κB goes into the nucleus and regulates the expression of other genes, including those involved in inflammation. NGF treatment reduced this effect, with less NF-κB found in the nuclei of NGF-treated cells after TLR3 activation.

TLR3 activation also led HCECs to produce inflammatory cytokines, messenger proteins such interleukin (IL)-6 and IL-8, which help drive inflammation, as well as more reactive oxygen species. These are highly reactive molecules that can cause damage to sub-cellular structures and are “weaponized” by the immune system against invaders such as viruses and bacteria. NGF treatment significantly reduced both of these effects.

“Taken together, this study indicates that NGF could inhibit TLR3-induced [inflammation] in HCECs, suggesting NGF as a potential therapeutic agent for HSK,” the researchers said.