Therapy for Ocular Toxoplasmosis – The Future

Garweg, Justus G.; Stanford, Miles

doi:10.3109/09273948.2013.779724

Cited by 25 publications

(15 citation statements)

References 55 publications

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“…Thus, possible reactivation of these ocular infections in postnatally infected individuals poses a hitherto underestimated problem for the health systems in these countries (2) and even more so in regions like South America (3,4). At the moment, no treatment has so far achieved a consistently reduced risk of reactivation, except perhaps in high-risk patients (5,6). To establish more specific, immune-based interventions, we need to elucidate the physiopathology of OT, which is so far largely ignored.…”

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confidence: 99%

Interleukin-6-Driven Inflammatory Response Induces Retinal Pathology in a Model of Ocular Toxoplasmosis Reactivation

et al. 2015

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c Ocular inflammation is one of the consequences of infection with the protozoan parasite Toxoplasma gondii. Even if lesions are self-healing in immunocompetent persons, they pose a lifetime risk of reactivation and are a serious threat to vision. As there are virtually no immunological data on reactivating ocular toxoplasmosis, we established a model of direct intravitreal injection of parasites in previously infected mice with a homologous type II strain. Two different mouse strains with variable ability to control retinal infection were studied in order to describe protective and deleterious reaction patterns. In Swiss-Webster mice, which are already relatively resistant to primary infection, no peak of parasite load was observed upon reinfection. In contrast, the susceptible inbred strain C57BL/6 showed high parasite loads after 7 days, as well as marked deterioration of retinal architecture. Both parameters were back to normal on day 21. C57BL/6 mice also reacted with a strong local production of inflammatory and Th1-type cytokines, like interleukin-6 (IL-6), IL-17A, and gamma interferon (IFN-␥), while Swiss-Webster mice showed only moderate expression of the Th2 cytokine IL-31. Interestingly, rapid intraocular production of anti-Toxoplasma antibodies was observed in Swiss-Webster but not in C57BL/6 mice. We then localized the cellular source of different immune mediators within the retina by immunofluorescence. Finally, neutralization experiments of IFN-␥ or IL-6 demonstrated the respective protective and deleterious roles of these cytokines for parasite control and retinal integrity during reinfection. In conclusion, we developed and immunologically characterized a promising mouse model of reactivating ocular toxoplasmosis. O cular toxoplasmosis (OT), a sequel of infection with the apicomplexan parasite Toxoplasma gondii, is a major cause of visual impairment worldwide, responsible for 30 to 50% of posterior uveitis in immunocompetent people. While OT was considered until recently as being exclusively due to congenital infection, screening of Toxoplasma-seropositive persons in Europe and North America revealed that 1 to 2% of this population presents retinal toxoplasmic lesions (1). Thus, possible reactivation of these ocular infections in postnatally infected individuals poses a hitherto underestimated problem for the health systems in these countries (2) and even more so in regions like South America (3, 4). At the moment, no treatment has so far achieved a consistently reduced risk of reactivation, except perhaps in high-risk patients (5, 6). To establish more specific, immune-based interventions, we need to elucidate the physiopathology of OT, which is so far largely ignored. Therefore, we wanted to gather novel data on the immune responses involved in retinal T. gondii reactivation. The long-term objective of this model is to open new therapeutic perspectives of human OT.The main obstacle for thorough research of ocular reactivation is the absence of a suitable mouse model (4). After oral or intraper...

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confidence: 99%

Interleukin-6-Driven Inflammatory Response Induces Retinal Pathology in a Model of Ocular Toxoplasmosis Reactivation

et al. 2015

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“…62 Drugs for the treatment of OT should ideally be (1) parasiticidal, (2) concentrated inside the eye, (3) capable of penetrating cyst walls, (4) effective against bradyzoites and tachyzoites, and (5) well tolerated and without adverse effects. 63 As with other parasitic diseases, pharmacological agents need to cross multiple important biological barriers to be clinically effective against T. gondii. This includes the plasmatic membrane, the parasitic membrane, and the membranes of specific organelles (most likely in the intracellular fluid).…”

Section: Diagnosismentioning

confidence: 99%

Current Therapy of Acquired Ocular Toxoplasmosis: A Review

Lima

Saraiva²,

Saraiva

2015

Journal of Ocular Pharmacology and Therapeutics

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Caused by the parasite Toxoplasma gondii, ocular toxoplasmosis (OT) is the most common form of posterior infectious uveitis. Combined antiparasitic therapy is the standard treatment for OT, but several other schemes have been proposed. The purpose of the present study was to review the literature on the treatment of OT and provide ophthalmologists with up-to-date information to help reduce OT-related visual morbidity. In conclusion, no ideal treatment scheme was identified; currently prescribed therapeutic schemes yield statistically similar functional outcomes.

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“…The timing of initiation and the appropriate dose of corticosteroids are important to balance the suppression of the immune response to the parasite while minimizing the disease severity [70]. Corticosteroid therapy without antiparasitics may lead to large retinal lesions even in immunocompetent patients [71,72]. The baseline indications for the use of corticosteroids include severe vitreous inflammation, decreased vision, proximity of lesions to the fovea or optic disk and the large size of the active lesion [58].…”

Section: Treatment and Managementmentioning

confidence: 99%

Recent Developments in the Diagnosis and Treatment of Ocular Toxoplasmosis

Özgönül

Besirli²

2016

Ophthalmic Res

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Ocular toxoplasmosis, a chorioretinal infection with Toxoplasma gondii, is the most common etiology of posterior uveitis in many countries. Accurate diagnosis depends heavily on the characteristic clinical features of this disease, but atypical presentations, especially in immunocompromised patients, may create diagnostic challenges and lead to misdiagnosis and inappropriate treatment. Molecular biology techniques to diagnose ocular toxoplasmosis have been available for many years and are now accessible as standard laboratory tests in many countries. Aqueous humor or vitreous evaluation to detect parasite DNA by polymerase chain reaction or specific antibody may provide definitive evidence for rapid diagnosis. Oral pyrimethamine and sulfadiazine plus systemic corticosteroids are an effective therapy for ocular toxoplasmosis. Recent data supports the use of other treatment approaches, including intravitreal antibiotics. The aim of the present review is to discuss briefly the new diagnostic tools and treatment options for ocular toxoplasmosis.

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Therapy for Ocular Toxoplasmosis – The Future

Cited by 25 publications

References 55 publications

Interleukin-6-Driven Inflammatory Response Induces Retinal Pathology in a Model of Ocular Toxoplasmosis Reactivation

Interleukin-6-Driven Inflammatory Response Induces Retinal Pathology in a Model of Ocular Toxoplasmosis Reactivation

Current Therapy of Acquired Ocular Toxoplasmosis: A Review

Recent Developments in the Diagnosis and Treatment of Ocular Toxoplasmosis

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