Dataset Information

Inflammation-suppressing cornea-in-a-syringe with anti-viral GF19 peptide promotes regeneration in HSV-1 infected rabbit corneas.

ABSTRACT: Pathophysiologic inflammation, e.g., from HSV-1 viral infection, can cause tissue destruction resulting in ulceration, perforation, and ultimately blindness. We developed an injectable Cornea-in-a-Syringe (CIS) sealant-filler to treat damaged corneas. CIS comprises linear carboxylated polymers of inflammation-suppressing 2-methacryloyloxyethyl phosphorylcholine, regeneration-promoting collagen-like peptide, and adhesive collagen-citrate glue. We also incorporated GF19, a modified anti-viral host defense peptide that blocked HSV-1 activity in vitro when released from silica nanoparticles (SiNP-GF19). CIS alone suppressed inflammation when tested in a surgically perforated and HSV-1-infected rabbit corneal model, allowing tissue and nerve regeneration. However, at six months post-operation, only regenerated neocorneas previously treated with CIS with SiNP-GF19 had structural and functional features approaching those of normal healthy corneas and were HSV-1 virus-free. We showed that composite injectable biomaterials can be designed to allow regeneration by modulating inflammation and blocking viral activity in an infected tissue. Future iterations could be optimized for clinical application.

SUBMITTER: Simoliunas E

PROVIDER: S-EPMC10907611 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Inflammation-suppressing cornea-in-a-syringe with anti-viral GF19 peptide promotes regeneration in HSV-1 infected rabbit corneas.

Simoliunas Egidijus E Ruedas-Torres Inés I Jiménez-Gómez Yolanda Y Edin Elle E Aghajanzadeh-Kiyaseh Mozhgan M Zamani-Roudbaraki Mostafa M Asoklis Rimvydas R Alksne Milda M Thathapudi Neethi C NC Poudel Bijay K BK Rinkunaite Ieva I Asoklis Kasparas K Iesmantaite Monika M Ortega-Llamas Laura L Makselis Almantas A Munoz Marcelo M Baltriukiene Daiva D Bukelskiene Virginija V Gómez-Laguna Jaime J González-Andrades Miguel M Griffith May M

NPJ Regenerative medicine 20240301 1

Pathophysiologic inflammation, e.g., from HSV-1 viral infection, can cause tissue destruction resulting in ulceration, perforation, and ultimately blindness. We developed an injectable Cornea-in-a-Syringe (CIS) sealant-filler to treat damaged corneas. CIS comprises linear carboxylated polymers of inflammation-suppressing 2-methacryloyloxyethyl phosphorylcholine, regeneration-promoting collagen-like peptide, and adhesive collagen-citrate glue. We also incorporated GF19, a modified anti-viral host ...[more]

PMID: 38429307

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Project description:PurposeAlthough the mechanisms underlying herpes simplex virus type-1 (HSV-1) ocular infection have been extensively studied, the role of host microRNAs (miRNAs) in the pathobiology of herpetic keratitis (HK) is not well understood. The aim of this study was to identify endogenous miRNA regulators involved in the progression of HSV-1 ocular infection.MethodsC57BL/6 mice were infected with HSV-1 strain McKrae following epithelial debridement, and corneal miRNA profiles were analyzed at various time points using miRNA sequencing (miRNA-seq). The miRNA expression was measured at 2, 4, 6, and 10 days post-infection. Ingenuity Pathway Analysis (IPA) was used to identify immune pathways potentially targeted by differentially expressed miRNAs. The role of selected miRNAs in viral entry and replication was assessed by overexpression in murine embryonic fibroblasts (MEFs) and human corneal epithelial cells (HCEs).ResultsA total of 32 miRNAs at 2 days post-infection, 21 miRNAs at 4 days post-infection, 140 miRNAs at 6 days post-infection, and 27 miRNAs at 10 days post-infection showed significant changes in expression. IPA revealed that differentially expressed miRNAs targeted several immune pathways, including TLR and interferon signaling. Notably, mmu-miR-184-3p and mmu-let-7d-5p were upregulated, whereas mmu-miR-329-3p was down-regulated during infection. Functional assays demonstrated that overexpression of miR-329, but not miR-184-3p or miR-let-7d-5p, increased HSV-1 viral entry and replication in a dose-dependent manner. In contrast, miR-329 inhibition reversed these effects, suggesting its role as a pro-viral miRNA. Increased plaque formation and viral gB expression further confirmed miR-329's pro-viral role.ConclusionsOur findings suggest that miR-329 functions as a pro-viral miRNA by disrupting TLR9 signaling, thus facilitating HSV-1 replication. Inhibition of miR-329 enhances TLR9-mediated antiviral responses, highlighting the potential of targeting host miRNAs as a novel therapeutic strategy for managing viral keratitis.

Dataset Information

Inflammation-suppressing cornea-in-a-syringe with anti-viral GF19 peptide promotes regeneration in HSV-1 infected rabbit corneas.

Publications

Inflammation-suppressing cornea-in-a-syringe with anti-viral GF19 peptide promotes regeneration in HSV-1 infected rabbit corneas.

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