ovalbumin and Uveitis

The immune-privileged status of the anterior chamber of the eye is altered in experimentally induced intraocular inflammation and in the pigment dispersion syndrome of DBA/2J mice. However, the eye has developed multiple mechanisms to maintain ocular immune privilege even in the presence of intraocular inflammation.

Topics: Animals; Anterior Chamber; Autoimmune Diseases; Eye; Humans; Immune Tolerance; Mice; Ovalbumin; Transforming Growth Factor beta; Uveitis

T cells are essential for the development of uveitis and other autoimmune diseases. After initial activation, CD4+ lymphocytes express the co-stimulatory molecule OX40 that plays an important role in T cell proliferation. Cyclin dependent kinase 2 (CdK2) plays a pivotal role in the cell cycle transition from G1 to S phase. In addition, recent research has implicated CdK2 in T cell activation. Thus, we sought to test the immunosuppressive effect of roscovitine, a potent CdK2 inhibitor, on CD4+ T cell activation, proliferation, and function.. Mouse CD4+ T cells were activated by anti-CD3 and anti-CD28 antibodies. The expression of OX40, CD44, and CdK2 were analyzed by flow cytometry. In addition, cell cycle progression and apoptosis of control and roscovitine-treated T lymphocytes were measured by BrdU incorporation and annexin V assay, respectively. Furthermore, the immunoregulatory effect of roscovitine was evaluated in both ovalbumin-induced uveitis and experimental autoimmune uveitis (EAU) models.. In this study, we found that T cell activation induced OX40 expression. Cell cycle analysis showed that more CD4+OX40+ cells entered S phase than OX40- T cells. Concurrently, CD4+OX40+ cells had a higher level of CdK2 expression. Roscovitine treatment blocked activated CD4+ cells from entering S phase. In addition, roscovitine not only reduced the viability of CD4+ lymphocytes but also suppressed T cell activation and cytokine production. Finally, roscovitine significantly attenuated the severity of T cell-dependent, OX40-enhanced uveitis.. These results implicate CdK2 in OX40-augmented T cell response and expansion. Furthermore, this study suggests that roscovitine is a novel, promising, therapeutic agent for treating T cell-mediated diseases such as uveitis.

Topics: Animals; Antibodies; Autoimmune Diseases; CD28 Antigens; CD3 Complex; CD4-Positive T-Lymphocytes; Cell Proliferation; Cyclin-Dependent Kinase 2; G1 Phase; Gene Expression; Hyaluronan Receptors; Immunologic Factors; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Ovalbumin; Protein Kinase Inhibitors; Purines; Receptors, OX40; Roscovitine; S Phase; Uveitis

Although NKT cells have been implicated in diverse immunomodulatory responses, the effector mechanisms underlying the NKT cell-mediated regulation of pathogenic T helper cells are not well understood. Here, we show that invariant NKT cells inhibited the differentiation of CD4(+) T cells into Th17 cells both in vitro and in vivo. The number of IL-17-producing CD4(+) T cells was reduced following co-culture with purified NK1.1(+) TCR(+) cells from WT, but not from CD1d(-/-) or Jα18(-/-) , mice. Co-cultured NKT cells from either cytokine-deficient (IL-4(-/-) , IL-10(-/-) , or IFN-γ(-/-) ) or WT mice efficiently inhibited Th17 differentiation. The contact-dependent mechanisms of NKT cell-mediated regulation of Th17 differentiation were confirmed using transwell co-culture experiments. On the contrary, the suppression of Th1 differentiation was dependent on IL-4 derived from the NKT cells. The in vivo regulatory capacity of NKT cells on Th17 cells was confirmed using an experimental autoimmune uveitis model induced with human IRBP(1-20) (IRBP, interphotoreceptor retinoid-binding protein) peptide. NKT cell-deficient mice (CD1d(-/-) or Jα18(-/-) ) demonstrated an increased disease severity, which was reversed by the transfer of WT or cytokine-deficient (IL-4(-/-) , IL-10(-/-) , or IFN-γ(-/-) ) NKT cells. Our results indicate that invariant NKT cells inhibited autoimmune uveitis predominantly through the cytokine-independent inhibition of Th17 differentiation.

Topics: Adoptive Transfer; Animals; Antigens, CD1d; Autoimmune Diseases; CD4-Positive T-Lymphocytes; Cell Communication; Cell Count; Cell Differentiation; Cytokines; Disease Models, Animal; Eye; Eye Proteins; Interleukin-4; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Natural Killer T-Cells; Ovalbumin; Peptide Fragments; Retinol-Binding Proteins; Th1 Cells; Th17 Cells; Uveitis; Vaccination

Pertussis toxin (PTX), an exotoxin of Bordetella pertussis, enhances the development of experimental autoimmune diseases such as experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE) in rodent models. The mechanisms of the promotion of experimental autoimmune diseases by PTX may be based upon PTX-induced disruption of the blood eye/brain barriers facilitating the infiltration of inflammatory cells, the modulation of inflammatory cell migration and the enhancement of the activation of inflammatory cells. We hypothesized that the facilitation of experimental autoimmunity by PTX suggests that its influence on the in vivo immune response to auto-antigen may differ from its influence on non-self antigens.. We have evaluated the effect of PTX on the simultaneous generation of delayed type hypersensitivity (DTH) responses and autoimmune responses to uveitogenic interphotoreceptor retinoid binding protein peptide (IRBP161-180), encephalitogenic myelin oligodendrocyte glycoprotein peptide (MOG35-55) or ovalbumin (OVA). PTX injection of mice immunized to IRBP peptide161-180 led to (i) the development of EAU as shown by histopathology of the retina, (ii) pro-inflammatory cytokine production by splenocytes in response to IRBP peptide161-180, and (iii) symptomatic EAE in mice immunized with encephalitogenic MOG peptide35-55. However, mice that received PTX had a reduced DTH response to IRBP161-180 peptide or MOG peptide35-55 when challenged distal to the site affected by autoreactive T cells. Moreover, footpad challenge with MOG35-55 peptide reduced EAE in mice immunized with MOG peptide. In contrast, the use of PTX when immunizing with OVA protein or an OVA immunogenic peptide did not affect the DTH response to OVA.. The results suggest that that the reduced DTH response in mice receiving PTX may be specific for autoantigens and autoantigen-reactive T cells are diverted away from ectopic sites that received the autoantigen and towards the tissue site of the autoantigen.

Topics: Amino Acid Sequence; Animals; Autoantigens; Cell Movement; Cytokines; Encephalomyelitis, Autoimmune, Experimental; Eye Proteins; Female; Humans; Hypersensitivity, Delayed; Lymphocytes; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Myelin Proteins; Myelin-Associated Glycoprotein; Myelin-Oligodendrocyte Glycoprotein; Ovalbumin; Peptide Fragments; Pertussis Toxin; Retinol-Binding Proteins; Th1 Cells; Uveitis

T cell-mediated uveitis is strongly associated with many systemic inflammatory disorders. Th17 cells are a novel T cell subset characterized by production of interleukin (IL)-17. In this study, we used DO11.10 mice to investigate the role of IL-17 in the pathogenesis of uveitis. CD4(+) T cells in DO11.10 mice are genetically engineered to react with ovalbumin (OVA). IL-17 expression was determined by real-time PCR and ELISPOT. Uveitis was induced by intravitreal injection of OVA, and ocular inflammation was evaluated by intravital microscopy. OVA challenge significantly induced IL-17 production by DO11.10 splenocytes in vitro. Next, we examined whether OVA challenge could elicit local inflammation and induce IL-17 in vivo. OVA elicited marked neutrophil-predominant inflammatory cell infiltration in the eyes. This leukocyte influx was mediated by CD4(+) lymphocytes as evidenced by significant inhibition of the ocular inflammation by CD4+ depleting antibody. Compared to control mice, OVA treatment induced IL-17 expression. Moreover, anti-IL-17 antibody markedly reduced OVA-mediated ocular inflammation. Finally, the neutralization of IL-17 attenuated ocular expression of CXCL2 and CXCL5, two cytokines which are chemotactic for neutrophils. Our study suggests that IL-17 is implicated in the pathogenesis of this T cell-mediated model of uveitis in part through neutrophil chemotaxis as a downstream effect of IL-17.

Topics: Animals; CD4-Positive T-Lymphocytes; Chemokine CXCL5; Enzyme-Linked Immunosorbent Assay; Eye; Inflammation; Interleukin-17; Mice; Mice, Inbred BALB C; Mice, Transgenic; Microscopy; Neutrophils; Ovalbumin; Reverse Transcriptase Polymerase Chain Reaction; Uveitis

Uveitis is an inflammatory ocular disease characterized by the infiltration of T lymphocytes and other leukocytes into the eye. The recruitment of these inflammatory cells from systemic vasculature to ocular tissue is a well-coordinated multistep process including rolling, firm adhesion and transmigration. CXCL12 (SDF-1alpha) is an endothelial cell-derived cytokine interacting with CXCR4 and CXCR7, two chemokine receptors mainly expressed in T cells, neutrophils and monocytes. Recent studies have shown that CXCR4, CXCR7 and their ligand, CXCL12, are important for the regulation of leukocyte mobilization and trafficking. However, it is unclear whether these two chemokine receptors are implicated in the pathogenesis of uveitis. In this study, we used DO11.10 mice, whose CD4+ T cells are genetically engineered to react with ovalbumin (OVA), to investigate the role of CXCR4 and CXCR7 in an animal model of uveitis. Intravital microscopy revealed that intravitreal OVA challenge of DO11.10 mice caused the infiltration of both T cells and neutrophils. The invasion of these inflammatory cells coincided with the detection of transcriptional up-regulation of CXCR4 and CXCR7 in the eye. In addition, both real-time-PCR and immunohistochemistry revealed an enhanced expression of endothelial CXCL12. Furthermore, intraperitoneal injection of AMD3100 (a specific CXCR4 antagonist) significantly attenuated OVA-induced uveitis and CXCL12-mediated transwell migration. In contrast, intraperitoneal administration of CXCR7 neutralizing antibody did not significantly alter ocular infiltration of inflammatory cells caused by OVA challenge. Our data suggest that CXCR4 but not CXCR7 plays a critical role in antigen-induced ocular inflammation by facilitating leukocyte infiltration. This study not only enhances our knowledge of the immunopathological mechanism of uveitis but also provides a novel rationale to target CXCR4 as an anti-inflammatory strategy to treat uveitis.

Topics: Acute Disease; Animals; Antibodies, Neutralizing; Benzylamines; CD4-Positive T-Lymphocytes; Cell Migration Inhibition; Cell Movement; Chemokine CXCL12; Cyclams; Flow Cytometry; Gene Expression Regulation; Green Fluorescent Proteins; Heterocyclic Compounds; Immunohistochemistry; Mice; Mice, Inbred BALB C; Mice, Transgenic; Neutrophils; Ovalbumin; Receptors, CXCR; Receptors, CXCR4; Reverse Transcriptase Polymerase Chain Reaction; Uveitis

To investigate the efficacy of the B subunit of Escherichia coli heat-labile enterotoxin (EtxB) in the treatment of ocular autoimmune disease. Murine experimental autoimmune uveoretinitis (EAU) is an animal model of autoimmune posterior uveitis initiated by retinal antigen-specific Th1 and Th17 CD4(+) T cells, which activate myeloid cells, inducing retinal damage. EtxB is a potent immune modulator that ameliorates other Th1-mediated autoimmune diseases, enhancing regulatory T-cell activity.. EAU was induced in B10.RIII mice by immunization with peptide hIRBP(161-180). Disease severity was measured by clinical and histologic assessment, and functional responses of macrophages (Mphis) and T cells were assessed, both in vivo and in cocultures in vitro. EtxB was administered intranasally daily for 4 days, starting either 3 days before or 3 days after EAU induction.. Preimmunization treatment with EtxB protected mice from EAU, limiting both the number and the activation status of retinal infiltrating immune cells. Treatment after EAU induction did not alter the disease course, despite suppression of IFN-gamma. Although EtxB treatment of in vitro cocultures of T cells and Mphis increased IL-10 production, EtxB treatment in vivo increased the proportion and number of IL-17-producing CD4(+) cells infiltrating the eye.. EtxB preimmunization protects mice from EAU induction by inhibiting Th1 responses, but the resultant reduction in IFN-gamma responses by EtxB does not effect infiltration or structural damage in established EAU, where Th17 responses predominate. These data highlight the critical importance of the dynamics of T-cell phenotype and infiltration during EAU when considering immunomodulatory therapy.

Topics: Amino Acid Sequence; Animals; Autoimmune Diseases; Bacterial Toxins; Bone Marrow Cells; Cell Division; Disease Models, Animal; Enterotoxins; Escherichia coli Proteins; Macrophages; Mice; Mice, Inbred C57BL; Ovalbumin; Peptide Fragments; Retinitis; Retinol-Binding Proteins; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Th1 Cells; Uveitis

The immune privilege that exists in the eye is maintained by various mechanisms. One of the best studied is a form of systemic tolerance termed anterior chamber-associated immune deviation (ACAID). We have investigated the mechanisms by which ocular inflammation associated with the vitreous cavity (VC) is reduced, by injecting either ovalbumin (OVA) or allogeneic splenocytes into the VCs of mice, and assessed the effect of this on delayed type hypersensitivity (DTH) responses. After antigen inoculation into the VC, antigen-specific DTH responses were significantly impaired and we named this phenomenon 'vitreous cavity-associated immune deviation' (VCAID). VCAID could also be induced by inoculating antigen-pulsed macrophages into the VC. However, VCAID did not develop either in mice with inflamed eyes, whether as a result of experimental autoimmune uveitis or coadministration of interleukin (IL)-6 in the VC, or in knockout mice deficient for natural killer T (NKT) cells. Finally, we found that so-called 'hyalocytes' are the only cells present in the VCs of normal mice, uniformly distributed on the retinal surface. Interestingly, they express F4/80, suggesting that hyalocytes are candidate antigen-presenting cells (APCs) responsible for mediating VCAID. As for the anterior chamber model, systemic tolerance can be induced in the VC in non-inflamed eyes and in the presence of invariant NKT cells.

Topics: Animals; Antigen-Presenting Cells; Antigens; Antigens, CD1; Antigens, CD1d; Autoimmune Diseases; Female; Hypersensitivity, Delayed; Immune Tolerance; Interleukin-6; Killer Cells, Natural; Macrophages; Mice; Mice, Inbred C57BL; Microscopy, Electron; Ovalbumin; Retina; Spleen; Uveitis; Vitreous Body

To determine whether the inflammation of endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU) alters key in vivo and in vitro parameters of ocular immune privilege.. For EIU induction, C3H/HeN mice received 200 microg lipopolysaccharide (LPS). For EAU induction, B10.A mice were immunized with 50 microg interphotoreceptor retinoid-binding protein (IRBP) mixed with complete Freund's adjuvant. Aqueous humor (AqH) was collected at periodic intervals and assayed for leukocyte content and the ability to suppress or enhance T-cell proliferation. Eyes with EAU were assessed for the capacity to support anterior chamber (AC)-associated immune deviation (ACAID) induction after injection of ovalbumin (OVA).. Inflammation within the anterior segment in EIU peaked at 12 to 24 hours and was detected from 10 days onward in EAU. In AqH of EIU, protein content rose within 4 hours, followed by infiltrating leukocytes. EIU AqH promptly lost its capacity to suppress T-cell proliferation and became mitogenic for T cells. In AqH of EAU, protein and leukocyte content rose at 11 days and continued to remain elevated thereafter. Whereas 11-day EAU AqH failed to suppress T-cell proliferation, AqH at later time points reacquired immunosuppressive properties. Injection of OVA into the AC of eyes of mice with EAU failed to induce ACAID.. The intraocular inflammation of EIU and EAU disrupted important parameters of immune privilege, ranging from breakdown of the blood- ocular barrier, to loss of an immunosuppressive microenvironment, to abrogation of ACAID. Because AqH from inflamed EAU reacquired the ability to suppress T-cell proliferation, the authors conclude that the capacity to regulate immune expression and inflammation can be a property even of inflamed eyes.

Topics: Animals; Anterior Eye Segment; Aqueous Humor; Autoimmune Diseases; Blood-Aqueous Barrier; Eye Proteins; Hypersensitivity, Delayed; Inflammation; Leukocyte Count; Lipopolysaccharides; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Ovalbumin; Retinitis; Retinol-Binding Proteins; Salmonella typhimurium; T-Lymphocytes; Uveitis

The purpose of this study was to assess the activity of some marketed products in ocular non-immune and immune type I hypersensitivity reactions, and during intra-ocular type III hypersensitivity. In order to compare these activities, we improved and validated three different models of ocular allergic reaction already known for their ability to reproduce allergic conjunctivitis or uveitis. Allergic conjunctivitis was induced by ocular immediate hypersensitivity after instillation of compound 48/80 in the rat, or an active anaphylaxis reaction with ovalbumin immunisation and challenge in the guinea pig. Uveitis was induced by a reverse passive anaphylaxis reaction using intra-vitreal rabbit anti-bovine IgG anti-serum sensitisation and intravenous bovine gamma-globulin challenge in the rabbit. Clinical scores and blood-tissue permeability indices were studied. Using the same schedule of ocular instillation, the effects of Livostin (levocabastine 0.05%), Almide (lodoxamide 0.1%), Opticrom (sodium cromoglycate 2%), Ocufen (flurbiprofen 0.03%), Acular (ketorolac 0.5%) and 0.3% chlorpheniramine maleate were compared to positive and negative controls. We demonstrated the potent activity of chlorpheniramine maleate 0.3% and Livostin in both allergic conjunctivitis models. Significant activity was also evidenced with Almide, which was only active in the non-immune allergy model, while Opticrom was definitely not active in these models. In the uveitis model, Acular and Ocufen are active and potent drugs, while Livostin and Almide were not active. These results are discussed with respect to the models used and the mediators involved.

Topics: Anaphylaxis; Animals; Blood Proteins; Capillary Permeability; Conjunctivitis, Allergic; Disease Models, Animal; Evans Blue; Guinea Pigs; Hypersensitivity, Immediate; Iris; Male; Ovalbumin; p-Methoxy-N-methylphenethylamine; Passive Cutaneous Anaphylaxis; Rabbits; Rats; Rats, Wistar; Uveitis

Oral administration of retinal soluble antigen (S-Ag) suppresses the induction of S-Ag-mediated experimental autoimmune uveitis (EAU) in Lewis rats. EAU induced with interphotoreceptor retinoid-binding protein (IRBP), another retinal autoantigen, can also be suppressed by oral administration of IRBP. It has been speculated that feeding with one retinal autoantigen could suppress induction of uveitis with the other retinal protein by means of bystander suppression. Both uveitogenic effector and suppressor cells should find their antigens within the retina, where the suppressor cells would be expected to act on the effector cells. However, reciprocal combinations of antigens used for induction and suppression of uveitis failed to prevent onset of disease, demonstrating that bystander suppression obviously does not occur in the eye. To investigate further the localization of suppressor mechanisms, we fed Lewis rats either with retinal S-Ag or with ovalbumin (OVA) and then immunized the animals either with a mixture of S-Ag and OVA or with each antigen separately, injected into contralateral hind legs. Feeding of S-Ag prior to immunization led to suppression of uveitis, whereas feeding of OVA had no tolerizing effect when S-Ag and OVA were injected into different legs. Nevertheless, immunizing rats with a mixture of S-Ag and OVA after OVA feeding suppressed uveitis to a high degree. These findings suggest that orally induced bystander suppression might not occur in the target organ, but rather peripherally at the site of induction of the autoimmune T cells.

Topics: Administration, Oral; Animals; Anterior Chamber; Antigens; Arrestin; Autoimmune Diseases; Cells, Cultured; Desensitization, Immunologic; Eye; Eye Proteins; Hindlimb; Immune Tolerance; Immunization; Injections, Subcutaneous; Lymph Nodes; Lymphocyte Activation; Ovalbumin; Rats; Rats, Inbred Lew; Retinitis; Retinol-Binding Proteins; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory; Tail; Uveitis

We compared the time course of changes in serum levels of circulating immune complexes (CICs) and of IgG antibody after sensitization of albino Lewis and pigmented Lister strain rats with uveitogenic (retinal S-antigen) and non-uveitogenic (ovalbumin) protein antigens of comparable molecular weight. Normal levels of CICs were far lower in Lewis rats in which experimental autoimmune uveoretinitis (EAU) takes the form of a severe panuveitis, than in Lister rats, in which the disease is mild, focal, confined to the posterior segment, and of lower incidence. After sensitization with either S-antigen or ovalbumin, polyethylene-glycol-precipitable CIC (PEG-CIC) peaked and fell as IgG antibody levels rose in both rat strains. However, peak levels of PEG-CIC were lower and subsequent IgG antibody levels were higher in the Lewis strain than in the less susceptible Lister strain. In both strains of rat these linked PEG-CIC/IgG antibody responses occurred earlier after sensitization with uveitogenic (S-) antigen than with ovalbumin, whether or not individual S-antigen-sensitized Lister rats developed EAU. In contrast, complement-binding CIC rose substantially only in those rats of both strains displaying EAU in response to S-antigen and not in response to ovalbumin. We suggest that immune complex (idiotypic) regulation of IgG antibody responses may be more readily perturbed by a pathogenic autoantigen (S-antigen) than by a bland antigen (ovalbumin). We also suggest that differences between the balance of regulatory and pathogenic CIC responses to uveitogenic retinal antigen may underlie or reflect strain differences in susceptibility to and severity of EAU.

Topics: Animals; Antigen-Antibody Complex; Antigens; Arrestin; Autoimmune Diseases; Enzyme-Linked Immunosorbent Assay; Eye Proteins; Freund's Adjuvant; Immunoglobulin G; Male; Ovalbumin; Rats; Rats, Inbred Lew; Retinitis; Species Specificity; Uveitis

Rabbit eye aqueous humor contains lysolecithin (LPC); the LPC concentration markedly increases, if the integrity of the hemato-aqueous barrier is impaired. It is assumed that LPC plays a causal role in the development of cataract because of its detergent action. We have studied the mechanism of LPC cumulation in the aqueous after a mechanical, endotoxic or immunological damage to the hemato-aqueous barrier. We measured in aqueous samples the activity of lecithin cholesterol acyltransferase (LCAT, EC 2.3.1.43), an enzyme which produces LPC and cholesteryl esters in the plasma. The transfer of phospholipids from the plasma into the aqueous was examined in vivo in 32p-prelabeled rabbits. Whereas LCAT was absent in the aqueous humor of intact eyes, an increased transesterification activity could be detected in all cases of impaired hemato-aqueous barrier. The proportion of LPC in aqueous phospholipids was similar to that found in high density lipoproteins, whereas whole plasma and low density lipoproteins contained a much lower proportion of LPC. An increased plasma level of LPC induced by the treatment of rabbits with phospholipase A2 in vivo, did not by itself lead to a preferential passage of plasma LPC through the blood-aqueous barrier. The experimental results rather imply that an impaired blood-aqueous barrier permitted an enhanced transfer from the plasma of intact HDL carrying also LPC and LCAT, and that the enzyme subsequently produced increased amounts of LPC in situ.

Topics: Animals; Aqueous Humor; Cholesterol; Endotoxins; Eye Injuries; Female; Lysophosphatidylcholines; Ovalbumin; Phosphatidylcholine-Sterol O-Acyltransferase; Phospholipids; Rabbits; Uveitis

The production of soluble lymphokine products of T lymphocytes was studied in the aqueous of rabbits with uveitis induced by intravitreal injection of 2.0 mg of ovalbumin. Aqueous from uveitic eyes demonstrated Ia-inducing activity at a dilution of 1:50 which diluted out at 1:250. The control aqueous and sera from normal or uveitic animals were negative. While production of interleukin 2(IL-2) in uveitic eyes could not be demonstrated in vitro, control rabbit concanavalin A-induced supernatants of nylon-wool-purified T cells contained both Ia-inducing and IL-2 activity. These data demonstrate antigen-driven production of a lymphokine activity in the aqueous of the uveitic eye. Local production of lymphokine may be a potent mechanism for amplification of the inflammatory process in uveitis.

Topics: Animals; Aqueous Humor; Cells, Cultured; Genes, MHC Class II; Histocompatibility Antigens Class II; Lymphokines; Macrophages; Ovalbumin; Rabbits; Reference Values; T-Lymphocytes; Uveitis

Topics: Animals; Antibody Formation; Eye; Hypersensitivity; Ovalbumin; Rabbits; Uveitis

We developed an experimental model of anterior uveitis by injecting ovalbumin or bovine serum albumin into the anterior chamber of sensitized rabbits. All the eyes showed leakage of serum proteins into the aqueous humor within 30 min. and developed uveitis within 24 hrs. which lasted at least a week. On histological examination, large numbers of polymorphonuclear (PMN) leucocytes and only occasional mononuclear cells were seen in the iris, the ciliary body and the irido-corneal angle. Immunohistological examination revealed 7s gamma globulin in the walls of blood vessels, in the interstitium and inside the PMN leucocytes. Contact radiographs of eyes challenged repeatedly showed extensive neovascularization of the iris and ciliary body.

Topics: Animals; Anterior Chamber; Antigens; Disease Models, Animal; Female; Fluorescent Antibody Technique; Immune Complex Diseases; Immunoglobulin G; Intradermal Tests; Ovalbumin; Precipitins; Rabbits; Serum Albumin, Bovine; Uvea; Uveitis

An egg albumin uveitis of the Arthus active type was developed in the rabbit. The experimental conditions were investigated in detail with regard to the following factors: influence of the number of sensitizing injections on serum antibody production, length of the recovery period which elapsed between sensitization and challenge, and influence of the size of the challenging dose on the severity of the inflammatory response. To develop the procedure optimally, emphasis was given to criteria of evaluation. Refractive index, protein and immunoglobulin assays in the aqueous humor of inflamed eyes were significantly correlated. These objective measures were considered more reliable than arbitrary grading systems. In addition, supportive histopathologic observations have been made in rabbit eyes. The above studies led to a reproducible model of uveitis in which drugs were tested topically. Dexamethasone phosphate in solution and indomethacin in suspension were effective in a dose-related manner. 6-Mercaptopurine did not demonstrate a useful anti-inflammatory effect.

Topics: Administration, Topical; Animals; Antibodies; Aqueous Humor; Arthus Reaction; Dexamethasone; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Eye Proteins; Female; Immunoglobulins; Indomethacin; Male; Mercaptopurine; Ovalbumin; Rabbits; Uveitis

Topics: Animals; Antibody Formation; Antibody Specificity; Antibody-Producing Cells; B-Lymphocytes; Cattle; Chickens; Eye; gamma-Globulins; Immunization, Secondary; Immunochemistry; Immunoglobulins; Immunologic Memory; Lymphokines; Ovalbumin; Rabbits; Uveitis

Topics: Animals; Cell Division; Cell Movement; Colchicine; Mitosis; Monocytes; Ovalbumin; Rabbits; Uveitis; Vitreous Body

Topics: Animals; Anterior Chamber; Antibodies; Antigen-Antibody Complex; Corneal Opacity; Eye; Female; gamma-Globulins; Graft vs Host Reaction; Immunity; Immunodiffusion; Iritis; Leukocytes; Lymph Nodes; Male; Ovalbumin; Plasma Cells; Rabbits; Skin Tests; Transplantation, Autologous; Transplantation, Homologous; Uveitis

Topics: Animals; Cornea; Corneal Transplantation; Female; Graft Rejection; Male; Ovalbumin; Prognosis; Rabbits; Skin Transplantation; Transplantation Immunology; Transplantation, Autologous; Transplantation, Homologous; Uveitis

Topics: Animals; Aqueous Humor; Cats; Colon; In Vitro Techniques; Iris; Ovalbumin; Prostaglandins; Rabbits; Rats; Tissue Extracts; Uveitis

Topics: Agglutination Tests; Animals; Antibodies; Antibody Formation; Antigens; Aqueous Humor; Ovalbumin; Rabbits; Staphylococcal Infections; Staphylococcus; Streptococcus; Uveitis; Vitreous Body

Topics: Animals; Antilymphocyte Serum; Horses; Hypersensitivity; Injections; Injections, Intramuscular; Injections, Intravenous; Ovalbumin; Rabbits; Uveitis; Vitreous Body

Topics: Adrenal Cortex Hormones; Animals; Anterior Chamber; Antilymphocyte Serum; Globulins; Immunosuppressive Agents; Injections; Ovalbumin; Rabbits; Uveitis