Pathogenic Role of Retinal Microglia in Experimental Uveoretinitis

Rao, Narsing A.; Kimoto, Takashi; Zamir, Ehud; Giri, Ranjit K.; Wang, Robert; Ito, Shinji; Pararajasegaram, Geeta; Read, Russell W.; Wu, Guey-Shuang

doi:10.1167/iovs.02-0199

Cited by 90 publications

(72 citation statements)

References 25 publications

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“…This was confirmed in our study, because retinal cells transduced with HA activated HA-specific T cells in the absence of exogenous HA. Importantly, not only were HAspecific T cells present in the affected eye, but also recipient T cells and numerous macrophages that have pathogenic roles in EAU (11,47,48). In addition, we were able to detect for the first time IFN-␥ and TNF-␣ cytokines directly in the eyes of mice.…”

Section: Discussionmentioning

confidence: 99%

Regulatory T Cells Control Uveoretinitis Induced by Pathogenic Th1 Cells Reacting to a Specific Retinal Neoantigen

Terrada

Fisson

Kozak³

et al. 2006

The Journal of Immunology

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In many clinical cases, uveitis develops secondary to an infection. This could result from peripheral activation followed by ocular penetration and reactivation of T cells specific for microbial Ags expressed in the retina. To gain insights into the pathophysiology of uveitis, we developed a new mouse model based on stable retinal expression of influenza virus hemagglutinin (HA) neoantigen by adeno-associated virus-mediated gene transfer. One month thereafter, we adoptively transferred HA-specific T cells, which were activated in vitro or in vivo. Intraocular inflammation was clinically and histologically observed in all animals within 15 days. The ocular infiltrate was composed mostly of macrophages and HA-specific T cells with a proinflammatory cytokine profile. Depletion of CD4+CD25+ regulatory T cells exacerbated the disease, whereas HA-specific CD4+CD25+ T cells given i.v. controlled the disease. This novel model should allow to better study the pathophysiology and therapeutic of uveitis.

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Section: Discussionmentioning

confidence: 99%

Regulatory T Cells Control Uveoretinitis Induced by Pathogenic Th1 Cells Reacting to a Specific Retinal Neoantigen

Terrada

Fisson

Kozak³

et al. 2006

The Journal of Immunology

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“…Myeloid cell activation in the retina is regulated by a tonic break functioning to prevent overt activation but maintain a scavenger function for daily housekeeping. The argument as to whether microglia contribute to onset of ocular inflammation 6 is balanced against their homoeostatic role in maintaining a healthy retina, and where data were supportive. 2 Microglia form a network throughout the retina, and display regulatory phenotypes and functions consistent with other tissue-resident macrophages elsewhere in the body.…”

Section: Keeping the Peacementioning

confidence: 99%

Doyne lecture 2016: intraocular health and the many faces of inflammation

Dick

2016

Eye

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Dogma for reasons of immune privilege including sequestration (sic) of ocular antigen, lack of lymphatic and immune competent cells in the vital tissues of the eye has long evaporated. Maintaining tissue and cellular health to preserve vision requires active immune responses to prevent damage and respond to danger. A priori the eye must contain immune competent cells, undergo immune surveillance to ensure homoeostasis as well as an ability to promote inflammation. By interrogating immune responses in non-infectious uveitis and compare with age-related macular degeneration (AMD), new concepts of intraocular immune health emerge. The role of macrophage polarisation in the two disorders is a tractable start. TNF-alpha regulation of macrophage responses in uveitis has a pivotal role, supported via experimental evidence and validated by recent trial data. Contrast this with the slow, insidious degeneration in atrophic AMD or in neovasular AMD, with the compelling genetic association with innate immunity and complement, highlights an ability to attenuate pathogenic immune responses and despite known inflammasome activation. Yolk sac-derived microglia maintains tissue immune health. The result of immune cell activation is environmentally dependent, for example, on retinal cell bioenergetics status, autophagy and oxidative stress, and alterations that skew interaction between macrophages and retinal pigment epithelium (RPE). For example, dead RPE eliciting macrophage VEGF secretion but exogenous IL-4 liberates an anti-angiogenic macrophage sFLT-1 response. Impaired autophagy or oxidative stress drives inflammasome activation, increases cytotoxicity, and accentuation of neovascular responses, yet exogenous inflammasome-derived cytokines, such as IL-18 and IL-33, attenuate responses.

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“…In early experimental autoimmune uveitis (EAU), microglial migration to and activation at photoreceptor leads to the generation of TNF-α and peroxynitrite prior to infiltration of macrophages, suggesting that microglia might initiate EAU pathogenesis [76]. Whether microglia initiate the recruitment of cells and cause amplification of inflammation is unclear.…”

Section: Microglia In Amdmentioning

confidence: 99%

Immunopathological aspects of age-related macular degeneration

2008

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Age-related macular degeneration (AMD) represents a leading cause of blindness worldwide. While the clinical and histopathological aspects of AMD are well characterized, its etiology and pathogenesis remain unclear. Recent findings suggest a role for immunologic processes in AMD pathogenesis, including the age-related generation of extracellular deposits inside the Brusch membrane and beneath the retinal pigment epithelium, recruitment of macrophages for clearance of these deposits, complement activation, recruitment of tissue-destructive macrophages, microglial activation and accumulation, and proinflammatory effects of chronic inflammation by Chlamydia pneumoniae. This review discusses the evidence for the role of inflammation in human AMD and in animal models of AMD.

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Pathogenic Role of Retinal Microglia in Experimental Uveoretinitis

Cited by 90 publications

References 25 publications

Regulatory T Cells Control Uveoretinitis Induced by Pathogenic Th1 Cells Reacting to a Specific Retinal Neoantigen

Regulatory T Cells Control Uveoretinitis Induced by Pathogenic Th1 Cells Reacting to a Specific Retinal Neoantigen

Doyne lecture 2016: intraocular health and the many faces of inflammation

Immunopathological aspects of age-related macular degeneration

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