LAUSR

ABSTRACT Herpes simplex virus type‐1 (HSV‐1) infection leads to impaired corneal sensation and, in severe cases, to corneal ulceration, melting and perforation. Here, we explore the potential therapeutic action of pigment epithelial‐derived factor (PEDF) plus docosahexaenoic acid (DHA) on corneal inflammation and nerve regeneration following HSV‐1 infection. Rabbits inoculated with 100,000 PFU/eye of HSV‐1 strain 17Syn+ were treated with PEDF + DHA or vehicle. PEDF + DHA treatment resulted in a biphasic immune response with stronger infiltration of CD4+T cells, neutrophils and macrophages at 7‐days post‐treatment (p.t.) that was significantly decreased by 14 days, compared to the vehicle‐treated group. Screening of 14 immune‐related genes by q‐PCR showed that treatment induced higher expression of IFN‐&ggr; and CCL20 and inhibition of IL‐18 by 7 days in the cornea. PEDF + DHA‐treated animals developed less dendritic corneal lesions, opacity and neovascularization. Corneal nerve density increased at 12‐weeks p.t. with functional recovery of corneal sensation. Treatment with PEDF + DHA that was postponed by 3 weeks also showed increased nerve density when compared to vehicle. Our data demonstrate that PEDF + DHA promotes resolution of the inflammatory response to the virus and, most importantly, induces regeneration of damaged corneal nerves vital for maintaining ocular surface homeostasis. HIGHLIGHTSPEDF + DHA treatment to rabbit corneas with acute HSV‐1 infection restores sensitivity.The treatment regenerates corneal nerves highly damage by HSV‐1 infection.There is a biphasic immune‐inflammatory reaction.As a result there is decreased corneal lesions, opacity and neovascularization in treated rabbits.