Topical antisense-oligonucleotides targeting IFN-gamma mRNA improve incidence and severity of herpetic stromal keratitis by cytokine specific and sequence unspecific effects

Wasmuth, Susanne; Bauer, Dirk; Steuhl, Klaus‐Peter; Heiligenhaus, Arnd

doi:10.1007/s00417-007-0707-1

Cited by 7 publications

(5 citation statements)

References 35 publications

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“…Viral loads of infected eyes were measured on day 5 post infection with a standard plaque assay (N = 6 in each group) [ 30 ]. The inflammatory cells in the corneas were counted as previously described [ 31 ]. Total cell numbers in spleens and lymph nodes were counted after the homogenization of the organs with a 70 µm cell strainer (BD Biosciences, Franklin Lakes, NJ, USA).…”

Section: Methodsmentioning

confidence: 99%

Prevention of Herpes Simplex Virus Induced Stromal Keratitis by a Glycoprotein B-Specific Monoclonal Antibody

et al. 2015

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The increasing incidence of acyclovir (ACV) and multidrug-resistant strains in patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis (HSK) is a major health problem in industrialized countries and often results in blindness. To overcome this obstacle, we have previously developed an HSV-gB-specific monoclonal antibody (mAb 2c) that proved to be highly protective in immunodeficient NOD/SCID-mice towards genital infections. In the present study, we examined the effectivity of mAb 2c in preventing the immunopathological disease HSK in the HSK BALB/c mouse model. Therefore, mice were inoculated with HSV-1 strain KOS on the scarified cornea to induce HSK and subsequently either systemically or topically treated with mAb 2c. Systemic treatment was performed by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure prophylaxis) or 24, 40, and 56 hours after infection (post-exposure immunotherapy). Topical treatment was performed by periodical inoculations (5 times per day) of antibody-containing eye drops as control, starting at 24 h post infection. Systemic antibody treatment markedly reduced viral loads at the site of infection and completely protected mice from developing HSK. The administration of the antiviral antibody prior or post infection was equally effective. Topical treatment had no improving effect on the severity of HSK. In conclusion, our data demonstrate that mAb 2c proved to be an excellent drug for the treatment of corneal HSV-infections and for prevention of HSK and blindness. Moreover, the humanized counterpart (mAb hu2c) was equally effective in protecting mice from HSV-induced HSK when compared to the parental mouse antibody. These results warrant the future development of this antibody as a novel approach for the treatment of corneal HSV-infections in humans.

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Section: Methodsmentioning

confidence: 99%

Prevention of Herpes Simplex Virus Induced Stromal Keratitis by a Glycoprotein B-Specific Monoclonal Antibody

et al. 2015

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“…IFN-γ is generally detected on 3 dpi in the inflamed sites of corneal stroma and lasts until 12 dpi (51). The treatment of HSK with antisense oligonucleotides targeting IFN-γ mRNA (IFN-γ-ASON) in vitro and in vivo obviously improves the incidence of HSK (52). However, another study demonstrated that IFN-γ has a dual role in the HSV-1-induced immune response.…”

Section: Regulation Of Anti-inflammatory Cytokines In Hskmentioning

confidence: 99%

Pathogenesis of Herpes Stromal Keratitis: Immune Inflammatory Response Mediated by Inflammatory Regulators

Wang

et al. 2020

Front. Immunol.

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Herpes stromal keratitis (HSK) is one of the primary diseases that cause vision loss or even blindness after herpes simplex virus (HSV)-1 infection. HSK-associated vision impairment is predominantly due to corneal scarring and neovascularization caused by inflammation. In the infected cornea, HSV can activate innate and adaptive immune responses of host cells, which triggers a cascade of reactions that leads to the release of inflammatory cytokines, chemokines, microRNA, and other regulatory factors that have stimulating or inhibitory effects on tissue. Physiologically, host cells show homeostasis. In this review, we summarize the factors involved in HSK pathogenesis from the perspective of immunity, molecules, and pathological angiogenesis. We also describe in detail the pathogenesis of chronic inflammatory lesions of the corneal stroma in response to HSV-1 infection.

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“…10 μL of 0.5% CSA/mPEGhexPLA micelle formulation contained 0.05 mg of CsA; the total administered drug dosage per mice averaged 0.25 mg of CsA/day (15.6 mg of CsA/kg/day). Because of the reconstitution of drug-loaded micelles in phosphate buffered solution and according to previous studies of topical regimen, ,,,− PBS was used as control treatment in this study.…”

Section: Methodsmentioning

confidence: 99%

Cyclosporine A-Loaded Nanocarriers for Topical Treatment of Murine Experimental Autoimmune Uveoretinitis

Kasper

Gabriel²,

Möller

et al. 2018

Mol. Pharmaceutics

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In the present study, tissue distribution and the therapeutic effect of topically applied cyclosporine A (CsA)-loaded methoxy-poly(ethylene-glycol)-hexyl substituted poly(lactic acid) (mPEGhexPLA) nanocarriers (ApidSOL) on experimental autoimmune uveitis (EAU) were investigated. The CsA-loaded mPEGhexPLA nanocarrier was tolerated well locally and showed no signs of immediate toxicity after repeated topical application in mice with EAU. Upon unilateral CsA treatment, CsA accumulated predominantly in the corneal and sclera-choroidal tissue of the treated eye and in lymph nodes (LN). This regimen reduced EAU severity in treated eyes compared to PBS-treated controls. This improvement was accompanied by reduced T-cell count, T-cell proliferation, and IL-2 secretion of cells from ipsilateral LN. In conclusion, topical treatment with CsA-loaded mPEGhexPLA nanocarriers significantly improves the outcome of EAU.

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Topical antisense-oligonucleotides targeting IFN-gamma mRNA improve incidence and severity of herpetic stromal keratitis by cytokine specific and sequence unspecific effects

Cited by 7 publications

References 35 publications

Prevention of Herpes Simplex Virus Induced Stromal Keratitis by a Glycoprotein B-Specific Monoclonal Antibody

Prevention of Herpes Simplex Virus Induced Stromal Keratitis by a Glycoprotein B-Specific Monoclonal Antibody

Pathogenesis of Herpes Stromal Keratitis: Immune Inflammatory Response Mediated by Inflammatory Regulators

Cyclosporine A-Loaded Nanocarriers for Topical Treatment of Murine Experimental Autoimmune Uveoretinitis

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