Intraocular Diseases – Anterior Uveitis

Bora, Nalini S.; Kaplan, Henry J.

doi:10.1159/000099272

Cited by 18 publications

(27 citation statements)

References 41 publications

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“…A recent report from the Northern California Epidemiology Study suggested a higher disease rate for the older population in the US. 1,2 Anterior uveitis (AU) is a term that refers to inflammation within the anterior segment of the eye; retinal involvement is not a component of AU. [1][2][3] Idiopathic AU is the most common form of intraocular inflammation in humans and the recurrent nature of the disease can lead to permanent visual loss.…”

Section: Experimental Autoimmune Anterior Uveitis (Eaau)mentioning

confidence: 99%

“…1,2 Anterior uveitis (AU) is a term that refers to inflammation within the anterior segment of the eye; retinal involvement is not a component of AU. [1][2][3] Idiopathic AU is the most common form of intraocular inflammation in humans and the recurrent nature of the disease can lead to permanent visual loss. [1][2][3] Idiopathic AU is a disease that is associated with significant morbidity and can only be treated symptomatically, but not cured.…”

Section: Experimental Autoimmune Anterior Uveitis (Eaau)mentioning

confidence: 99%

“…[1][2][3] Idiopathic AU is the most common form of intraocular inflammation in humans and the recurrent nature of the disease can lead to permanent visual loss. [1][2][3] Idiopathic AU is a disease that is associated with significant morbidity and can only be treated symptomatically, but not cured. Treatment options available to uveitis patients have limitations because uveitis is generally treated symptomatically with topical, periocular, or systemic administration of corticosteroids.…”

Section: Experimental Autoimmune Anterior Uveitis (Eaau)mentioning

confidence: 99%

“…Uveitis patients with severe unresponsiveness to corticosteroid may need immunosuppressive therapy. [1][2][3] Unfortunately, these therapies are associated with serious side effects. Therefore, continuous efforts and future investigations are needed so that uveitis could be prevented and efficient and safe therapies for the future could be developed.…”

Section: Experimental Autoimmune Anterior Uveitis (Eaau)mentioning

confidence: 99%

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Tolerance to Melanin-Associated Antigen in Autoimmune Uveitis Is Mediated by CD4+CD25+ T-Regulatory Cells

Matta

Jha

Bora

et al. 2008

The American Journal of Pathology

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Experimental autoimmune anterior uveitis (EAAU)serves as an animal model for human idiopathic AU, the most common form of intraocular inflammation of significant morbidity whose recurrence can lead to permanent vision loss. This study was undertaken to inhibit EAAU by inducing tolerance to melanin-associated antigen (MAA) and to investigate the underlying mechanisms responsible for tolerance induction. Intravenous administration of MAA both induced tolerance and inhibited EAAU in Lewis rats. Flow cytometric analysis revealed that the proliferation of lymph node cells in response to antigenic stimulation was drastically reduced in the state of tolerance both in vivo and in vitro. Our results from co-culture experiments demonstrated that intravenous administration of MAA led to the generation of T-regulatory cells that suppress T-cell proliferative responses and induce tolerance. Expression levels of both interleukin-10 and transforming growth factor-␤2 were elevated whereas reduced levels of tumor necrosis factor-␣, interferon-␥, and interleukin-2 were detected in tolerance-induced animals. Tolerance was reversed by replenishing these animals with recombinant interleukin-2. Tolerance could be adoptively transferred by removing lymph node cells from tolerance-induced donors and giving them to recipient rats. Interestingly, adoptive transfer of tolerance failed when lymph nodes cells were depleted of Uveitis is broadly defined as inflammation of the uvea and is responsible for more than 2.8% of blindness in the US.Each year, 17.6% of active uveitis patients experience a transient or permanent loss of vision. A recent report from the Northern California Epidemiology Study suggested a higher disease rate for the older population in the US.

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Section: Experimental Autoimmune Anterior Uveitis (Eaau)mentioning

confidence: 99%

Section: Experimental Autoimmune Anterior Uveitis (Eaau)mentioning

confidence: 99%

Section: Experimental Autoimmune Anterior Uveitis (Eaau)mentioning

confidence: 99%

Section: Experimental Autoimmune Anterior Uveitis (Eaau)mentioning

confidence: 99%

See 2 more Smart Citations

Tolerance to Melanin-Associated Antigen in Autoimmune Uveitis Is Mediated by CD4+CD25+ T-Regulatory Cells

Matta

Jha

Bora

et al. 2008

The American Journal of Pathology

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“…Anterior uveitis (AU) 2 refers to the inflammation of the anterior segment of the eye, which includes the iris and the ciliary body (CB). Idiopathic AU is the most common form of intraocular inflammation in humans (1)(2)(3). Experimental autoimmune anterior uveitis (EAAU) is an organ-specific autoimmune disease of the eye that serves as an animal model of noninfectious autoimmune idiopathic AU (4 -15).…”

mentioning

confidence: 99%

Inhibition of Complement Alternative Pathway Suppresses Experimental Autoimmune Anterior Uveitis by Modulating T Cell Responses

Manickam

Jha

Matta

et al. 2011

Journal of Biological Chemistry

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The objective of the current study was to delineate the pathway of complement activation that is crucial for the induction of experimental autoimmune anterior uveitis (EAAU). We studied the development of EAAU in melanin-associated antigen (MAA)-sensitized Lewis rats treated with antibody against C4 or factor B. Control animals received isotype IgG control. Antibody against C4 had no effect on EAAU, and all of the animals developed EAAU similar to those injected with control IgG. Uveitis, a vision-threatening intraocular inflammatory disease is one of the leading causes of vision loss worldwide. Anterior uveitis (AU) 2 refers to the inflammation of the anterior segment of the eye, which includes the iris and the ciliary body (CB). Idiopathic AU is the most common form of intraocular inflammation in humans (1-3). Experimental autoimmune anterior uveitis (EAAU) is an organ-specific autoimmune disease of the eye that serves as an animal model of noninfectious autoimmune idiopathic AU (4 -15). The EAAU model has been extensively used in our laboratory to understand the underlying mechanisms involved in the pathogenesis of idiopathic AU (5-15). In this experimental model, inbred Lewis rats are subcutaneously immunized in the footpad with melanin-associated antigen (MAA) isolated from the iris and the CB, and EAAU is induced in these animals by an antigen-specific CD4 ϩ T cell response to MAA (5-15). The hallmark pathologic features of EAAU include lymphocytic infiltration in the iris, the CB, and the anterior segment of the eye with no inflammation of the retina (5-15). Antigen-specific CD4 ϩ T cells can adoptively transfer disease into naïve syngenic recipients (7,8,13) and are the predominant inflammatory cells within the uvea (5-15).Previous reports from our laboratory have established a critical role of complement in EAAU (9, 10). Complement has been recognized as a key innate immune defense system that plays an important role in fighting infections and modulating various immune and inflammatory responses by bridging the innate immunity with adaptive immune responses (16 -21). The complement systems consist of more than 35 proteins circulating in blood and expressed on cell membranes. These proteins interact with one another in three distinctive activation cascades: the classical, the lectin, and the alternative, which can be triggered by different stimuli. Complement component 4 (C4) is a component of both the classical and lectin pathways, whereas factor B is the integral component of the alternative pathway (19 -21). Complement activation via these pathways is under strict control of complement regulatory proteins; disruption of the balance between complement activation and regulation can result in deleterious effects on the host and contributes to several diseases (22-36). Recently we have reported that suppression of complement activation by recombinant complement regulatory protein inhibits EAAU (15). However, the contribution of each complement activation pathway in EAAU has not yet been described. In this...

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The role of complement in ocular pathology

2008

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Functionally active complement system and complement regulatory proteins are present in the normal human and rodent eye. Complement activation and its regulation by ocular complement regulatory proteins contribute to the pathology of various ocular diseases including keratitis, uveitis and age-related macular degeneration. Furthermore, a strong relationship between age-related macular degeneration and polymorphism in the genes of certain complement components/complement regulatory proteins is now well established. Recombinant forms of the naturally occurring complement regulatory proteins have been exploited in the animal models for treatment of these ocular diseases. It is hoped that in the future recombinant complement regulatory proteins will be used as novel therapeutic agents in the clinic for the treatment of keratitis, uveitis, and age-related macular degeneration.

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Intraocular Diseases – Anterior Uveitis

Cited by 18 publications

References 41 publications

Tolerance to Melanin-Associated Antigen in Autoimmune Uveitis Is Mediated by CD4+CD25+ T-Regulatory Cells

Tolerance to Melanin-Associated Antigen in Autoimmune Uveitis Is Mediated by CD4+CD25+ T-Regulatory Cells

Inhibition of Complement Alternative Pathway Suppresses Experimental Autoimmune Anterior Uveitis by Modulating T Cell Responses

The role of complement in ocular pathology

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