%0 Journal Article
%A Lee, Chyan-Jang
%A Buznyk, Oleksiy
%A Kuffova, Lucia
%A Rajendran, Vijayalakshmi
%A Forrester, John V.
%A Phopase, Jaywant
%A Islam, Mohammad M.
%A Skog, Mårten
%A Ahlqvist, Jenny
%A Griffith, May
%T Cathelicidin LL-37 and HSV-1 Corneal Infection: Peptide Versus Gene Therapy
%B Translational Vision Science & Technology
%D 2014
%R 10.1167/tvst.3.3.4
%J Translational Vision Science & Technology
%V 3
%N 3
%P 4-4
%@ 2164-2591
%X    To evaluate the potential utility of collagen-based corneal implants with anti–Herpes Simplex Virus (HSV)-1 activity achieved through sustained release of LL-37, from incorporated nanoparticles, as compared with cell-based delivery from model human corneal epithelial cells (HCECs) transfected to produce endogenous LL-37.    We tested the ability of collagen-phosphorylcholine implants to tolerate the adverse microenvironment of herpetic murine corneas. Then, we investigated the efficacy of LL-37 peptides delivered through nanoparticles incorporated within the corneal implants to block HSV-1 viral activity. In addition, LL-37 complementary DNA (cDNA) was transferred into HCECs to confer viral resistance, and their response to HSV-1 infection was examined.    Our implants remained in herpetic murine corneas 7 days longer than allografts. LL-37 released from the implants blocked HSV-1 infection of HCECs by interfering with viral binding. However, in pre-infected HCECs, LL-37 delayed but could not prevent viral spreading nor clear viruses from the infected cells. HCECs transfected with the LL-37 expressed and secreted the peptide. Secreted LL-37 inhibited viral binding in vitro but was insufficient to protect cells completely from HSV-1 infection. Nevertheless, secreted LL-37 reduced both the incidence of plaque formation and plaque size.    LL-37 released from composite nanoparticle-hydrogel corneal implants and HCEC-produced peptide, both showed anti–HSV-1 activity by blocking binding. However, while both slowed down virus spread, neither was able on its own to completely inhibit the viruses.    LL-37 releasing hydrogels may have potential utility as corneal substitutes for grafting in HSV-1 infected corneas, possibly in combination with LL-37 producing therapeutic cells.  
%[ 2/26/2021
%U https://doi.org/10.1167/tvst.3.3.4