A murine model of herpes simplex virus-induced ocular disease for antiviral drug testing

Brandt, Curtis R.; Coakley, Leeanne M.; Grau, Dorene R.

doi:10.1016/0166-0934(92)90052-f

Cited by 35 publications

(30 citation statements)

References 16 publications

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“…Brandt et al (6) used mice to demonstrate that TFT at various topical doses could improve SLE scores and reduce viral titers in the eye and TG, as well as reduce reactivation in TG explant cultures. LeBlanc et al (32) also used mice to determine the efficacies of FCV and VCV and reported that the two drugs were equally effective in reducing viral titers in the eye and mortality rates; however, VCV was better than FCV at decreasing the viral load in the TG of FIG.…”

Section: Discussionmentioning

confidence: 99%

Effect of famciclovir on herpes simplex virus type 1 corneal disease and establishment of latency in rabbits

Loutsch

Sáinz²,

Marquart³

et al. 2001

American Journal of Ophthalmology

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Section: Discussionmentioning

confidence: 99%

Effect of famciclovir on herpes simplex virus type 1 corneal disease and establishment of latency in rabbits

Loutsch

Sáinz²,

Marquart³

et al. 2001

American Journal of Ophthalmology

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“…Examiners were masked regarding the genotype and viral infection status of each mouse. Corneal opacification and neovascularization were graded on a scale from 0 through 4 using a previously published scoring system with minor modifications (7,18). Corneal opacification was scored as follows: 0, normal/absent; 1, mild opacification, iris detail visible; 2, iris detail obscured; 3, cornea totally opaque; 4, cornea perforated.…”

Section: Animalsmentioning

confidence: 99%

Pathogenesis of Herpes Simplex Virus Type 1-Induced Corneal Inflammation in Perforin-Deficient Mice

Chang

Galle

Maggs

et al. 2000

J Virol

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Herpetic stromal keratitis (HSK) is an inflammatory disease of the cornea that often results in blindness.It is mediated by a host immune response which is triggered by herpes simplex virus (HSV) infection. Immune effector mechanisms are hypothesized to be important in disease development. We investigated, in a mouse model, whether perforin-dependent cytotoxicity is an important effector mechanism in the production of HSK. Wild-type (C57BL/6) and perforin-deficient (PKO) mice were infected intracorneally with HSV-1 strain F. Clinical disease and histologic lesions of the cornea at 23 days postinfection (p.i.) were significantly less severe in HSV-1-infected PKO mice than in infected wild-type mice. mRNA for the chemokine macrophage inflammatory protein 1␣ (MIP-1␣) was detected by reverse transcription-PCR in the corneas of infected wild-type mice but not in the corneas of infected PKO mice at 23 days p.i. Adoptive transfer of wild-type HSV-1 immune T-cell-enriched splenocytes into HSV-1-infected PKO mice restored the disease phenotype which was seen in infected wild-type mice. In contrast, mice carrying a null-function mutation in the Fas ligand, which is involved in an alternative cytotoxic mechanism, developed clinical disease and histologic lesions which were comparable to those in wild-type mice. Viral clearance from the eyes of PKO mice was not impaired. There was no significant difference between the infectious viral titers isolated from the eyes of PKO and wild-type mice. Our findings show that perforin is important in the pathogenesis of HSK.Herpetic stromal keratitis (HSK) is a chronic inflammation of the cornea which is a consequence of infection by herpes simplex virus (HSV). It is the main nontraumatic cause of corneal blindness in people in developed countries (54). HSV-1-induced corneal inflammation in the mouse model is an immunopathological condition mediated by T lymphocytes (11, 20-22, 38, 48, 49, 54). T-cell-deficient mice, such as athymic nude mice, scid mice, or thymectomized mice, do not develop keratitis following intracorneal infection with HSV-1. However, these mice develop HSK upon intracorneal HSV-1 infection if they have previously received an adoptive transfer of HSV-1 immune T lymphocytes (3,11,12,21,37,43,58).The main effector mechanisms mediated by T lymphocytes are the secretion of soluble factors such as cytokines and chemokines and the lysis of target cells. Cytokines, such as gamma interferon, have been proposed as mediators of HSK (2,20,24). However, studies of gamma interferon knockout mice failed to demonstrate a role for gamma interferon in the pathogenesis of HSV-induced stromal keratitis (5). Chemokines have also been postulated to be involved in the development of HSK (55, 57, 59). There is evidence that macrophage inflammatory protein 1␣ (MIP-1␣), a beta chemokine involved in lymphocyte recruitment, plays a role in the development of HSK (60).Immune cytotoxic effector mechanisms play a role in the development of many immune-mediated disorders. The two main cytotoxic ef...

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“…However, sometimes, episodes of herpetic ophthalmic disease result in the involvement of the deeper corneal tissue leading to corneal scarring with consequent reduction in visual acuity. Additionally, delay in the treatment of HSV-1 ophthalmic disease can lead to a more significant corneal scar, and topical steroid treatment in unsuspected active herpes ophthalmic can lead to corneal melting 3,4,6,10,11,15 .…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, we had previously optimized a murine model of HSV-1 ophthalmic disease, in which BALB/c mouse corneas were inoculated without trauma and with HSV-1 strain obtained from a patient with severe herpetic disease, to mimic the infection in humans 4,5,10,11,15 .…”

Section: Introductionmentioning

confidence: 99%

An immunofluorescence test for diagnosis of ophthalmic herpes in a mouse corneal model

Pereira

Câmara

Guimarães

et al. 2007

Rev. Inst. Med. trop. S. Paulo

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SUMMARYHerpes simplex virus type 1 (HSV-1) ophthalmic disease is the most common cause of corneal blindness in humans worldwide. Current culture techniques for HSV take several days and commercially available HSV laboratory based diagnostic techniques vary in sensitivity. Our study was conducted to evaluate the use of a quicker and simpler method to herpes ophthalmic diagnosis. Corneal smears were made by firm imprints of infected mouse eyes to glass slides, after smears were fixated with cold acetone, and an indirect immunofluorescence (IIF) method was performed using monoclonal antibodies in a murine model of ophthalmic herpes. Eye swabs from infected mice were inoculated in Vero cells for virus isolation. Cytology and histology of the eye were also performed, using hematoxylin-eosin routine. Mouse eyes were examined by slit-lamp biomicroscopy for evidence of herpetic disease at various times postinoculation. We made a comparative evaluation of sensitivity, specificity and speed of methods for laboratory detection of HSV. Our results indicate that this IIF method is quick, sensitive, specific and can be useful in the diagnosis of ophthalmic herpes as demonstrated in an animal model.

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A murine model of herpes simplex virus-induced ocular disease for antiviral drug testing

Cited by 35 publications

References 16 publications

Effect of famciclovir on herpes simplex virus type 1 corneal disease and establishment of latency in rabbits

Effect of famciclovir on herpes simplex virus type 1 corneal disease and establishment of latency in rabbits

Pathogenesis of Herpes Simplex Virus Type 1-Induced Corneal Inflammation in Perforin-Deficient Mice

An immunofluorescence test for diagnosis of ophthalmic herpes in a mouse corneal model

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