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Chyan-Jang Lee, Oleksiy Buznyk, Lucia Kuffova, Vijayalakshmi Rajendran, John V. Forrester, Jaywant Phopase, Mohammad M. Islam, Mårten Skog, Jenny Ahlqvist, May Griffith; Cathelicidin LL-37 and HSV-1 Corneal Infection: Peptide Versus Gene Therapy. Trans. Vis. Sci. Tech. 2014;3(3):4. doi: 10.1167/tvst.3.3.4.
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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.
Translational Relevance: :
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.
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