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Horses with recurrent uveitis can be treated by intravitreal injection of low dose gentamicin under sedation and after local anesthetic techniques including the retrobulbar nerve block. Since it is reported that retinal degeneration can be secondary to an acute increase of intraocular pressure (IOP), the current randomized controlled study was carried out in order to investigate the changes in IOP following retrobulbar anesthesia, with two different volumes of local anesthetic (lidocaine) solution (10 and 5 mL), and intravitreal injection of 6 mg gentamicin in two different volumes of solution (0.3 and 0.15 mL). Multivariate regression showed that IOP was significantly lower in the pathologic eye at baseline (estimated effect size -6.1 mmHg; P = .0001) and after sedation (estimated effect size -9.4 mmHg; P < .0001). The IOP was significantly higher after a 10 mL block (P .0002) but this effect was very small (+0.5 mmHg). There was no significant difference in IOP after the injection of 0.15 or 0.3 mL solution of gentamicin. There was no significant combined effect of the volume of local anesthetic used for the block and the volume of the gentamicin solution. Since the expected anesthetic effects (desensitization and akinesia) were met in all cases, the smaller volume of 5 mL of lidocaine solution would be preferable for retrobulbar block for intravitreal injections, while intravitreal injections volumes of 0.15 and 0.30 mL can be used indifferently., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Equine recurrent uveitis (ERU) is a spontaneous, remitting-relapsing autoimmune disease driven by the adaptive immune system. Although T cells are described as the main effector cells in pathogenesis, granulocytes have also emerged as possible disease mediators. To explore the role of these innate immune cells, we investigated the whole cell proteome of granulocytes from equine recurrent uveitis cases and healthy controls. Among the 2362 proteins identified by mass spectrometry, we found 96 proteins with significantly changed abundance between groups (p < 0.05, fold change >1.2), representing 4.1% of total granulocyte proteome. Within these differential identifications, calgranulin B, a protein associated with pathogenesis in other autoimmune diseases, showed highest abundance in equine recurrent uveitis (18 fold). For a better interpretation of the results from our hypothesis-generating approach, we added a threshold for biological significance (ratio ERU/controls >2: 36 proteins) to the proteins with increased abundance in equine recurrent uveitis and analyzed their allocation to the subsets within the Immune System superpathway. The 36 differentially abundant proteins predominantly associated to RAF/MAP kinase cascade, MHC-I-mediated antigen presentation and neutrophil degranulation, suggesting a latently activated phenotype of these innate immune cells in disease. Raw data are available via ProteomeXchange with identifier PXD013648. SIGNIFICANCE: Our study provides new insights into the protein repertoire of primary equine granulocytes and identifies protein abundance changes associated to equine recurrent uveitis (ERU), an organ specific, spontaneously occurring autoimmune disease. We show that granulocyte proteins with increased abundance in ERU strongly associate to RAF/MAP kinase signaling, MHC-I antigen presentation and neutrophil degranulation, pointing to a more activated state of these cells in ERU cases. Since cells were obtained in quiescent stage of disease, latent activation of granulocytes underlines the role of these innate immune cells in ERU. These findings are highly relevant for veterinary medicine, further establishing the importance of granulocytes in this T cell-driven autoimmune disease. Moreover, they have translational quality for autoimmune uveitis in man, due to strong similarity in disease occurrence, progression and pathogenesis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We report an unusual case of leishmaniosis with the involvement of mammary glands in an old cat with what seems to be a concurrent regressive feline leukemia virus infection. Leishmania donovani complex parasites were identified for the first time in inflammatory breast fluid during a clinical recurrence manifested about 4 years after the first diagnosis of feline leishmaniosis. Combined treatment with allopurinol and meglumine antimoniate resulted in clinical cure of mammary lesion and a concurrent uveitis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We report a retrospective evaluation of intravitreal gentamicin (6 mg in 0.3 mL solution) injection in 71 horses with equine recurrent uveitis between 2010 and 2016. Aqueous flare and hyalitis were scored at the baseline in all horses, then at 15, 30, 60, 90, 180, 365, and 730 in 37, 46, 30, 25, 22, 18, and 11 horses, respectively. Forty-two animals had a global score of inflammation (sum of scores for aqueous flare and hyalitis) of zero at the last examination (number of re-examinations per horse ranged from 1 to 5). Among the 29 remaining horses, four were not reassessed after the intervention. The individual inflammation scores of the remaining 25 horses improved in 21 cases, whereas it slightly deteriorated in four cases (number of re-examinations ranged from 0 to 6). Ocular hypotension, lens opacities, and retinal folds were observed, respectively, in 92%, 78%, and 28% of the 71 eyes at the baseline, and in 80%, 90%, and 36% of the 11 eyes re-evaluated at 2 years. A telephone inquiry about all horses among owners and referring veterinarians conducted in 2016 at least 6 months after the more recent injections indicated that 70 horses did not develop a new observable episode of inflammation and did not need ocular medication. Although the results of this study should be discussed with reservation, it indicated that low-dose intravitreal injection of gentamicin could be a useful treatment to maintain ocular quiescence in equine recurrent uveitis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The membrane protein expression repertoire of cells changes in course of activation. In equine recurrent uveitis (ERU), a spontaneous autoimmune disease in horses with relapsing and ultimately blinding inner eye inflammation, CD4+ T lymphocytes are the crucial pathogenic cells activated in the periphery directly prior to an inflammatory episode. In order to find relevant changes in the membrane proteome associated to disease, we sorted CD4+ lymphocytes and compared protein abundance from the generated proteome datasets of both healthy horses and ERU cases. We detected formin like 1, a key player in actin dependent cellular processes such as phagocytosis, cell adhesion and cell migration, with significantly higher abundance in the CD4+ cell membrane proteome of horses with ERU. In transmigration experiments, we demonstrated higher migration rate of cells originating from diseased animals connecting formin like 1 to the migratory ability of cells. These findings are the first description of formin like 1 in association to processes involved in migration of inflammatory CD4+ T cells across the blood-retinal barrier in a spontaneous ocular autoimmune disease and suggest formin like 1 to play a role in the molecular mechanisms of ERU disease pathogenesis. Data are available via ProteomeXchange with identifier PXD005384., Biological Significance: This comparative proteomic study of membrane proteins of CD4+ T cells identified a novel protein, formin like 1, with expression on the plasma cell membrane of equine CD4+ T cells and a significant change of abundance on CD4+ T cells of horses with a spontaneous autoimmune disease. Functional studies in a cell culture model for transmigration at the blood-retinal barrier (BRB) unraveled a strong impact of formin like 1 on migratory processes of CD4+ T cells across the BRB, a key event in uveitis pathogenesis. These findings provide novel knowledge about changes in the CD4+ immune cell membrane proteome in a spontaneously and naturally occurring autoimmune disease in horses with high relevance for veterinary medicine. Additionally, this model has proven translational quality for human medicine and provides novel proteomic information on autoimmune uveitis in man., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Emergencies involving the crystalline lens are not common; however, their clinical signs must be recognized quickly to begin treatment or referred immediately to improve the chances of retaining sight. The lens is a unique structure because of its immunologically privileged status and its imperative clarity for vision. Any insult to the lens capsule's integrity, its position within the globe, or to its clarity may result in undesirable sequelae., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye and plays an important role in pathogenesis of the sight threatening disease equine recurrent uveitis (ERU). ERU is a spontaneous autoimmune mediated inflammatory disease characterised by the breakdown of the outer blood-retinal barrier and an influx of autoaggressive T-cells into the inner eye. Therefore, identification of molecular mechanisms contributing to changed function of blood-retinal barrier in ERU is important for the understanding of pathophysiology. Cell surface proteins of RPE collected from healthy horses and horses with ERU were captured by in situ biotinylation and analysed with high resolution mass spectrometry coupled to liquid chromatography (LC-MS/MS) to identify differentially expressed proteins. With label free differential proteomics, a total of 27 differently expressed cell surface proteins in diseased RPE could be detected. Significant down-regulation of three very interesting proteins, synaptotagmin 1, basigin and collectrin was verified and further characterised., Biological Significance: We applied an innovative and successful method to detect changes in the plasma cell surface proteome of RPE cells in a spontaneous inflammatory eye disease, serving as a valuable model for human autoimmune uveitis. We were able to identify 27 differentially expressed plasma cell membrane proteins, including synaptotagmin 1, basigin and collectrin, which play important roles in cell adhesion, transport and cell communication., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Two horses with chronic uveitis and histological lesions consistent with equine recurrent uveitis (ERU) were examined. Microscopical findings in the ciliary body included deposits of amyloid lining the non-pigmented epithelium, intracytoplasmic, rod-shaped, eosinophilic inclusions and intraepithelial infiltration of T lymphocytes. Ultrastructural examination of the ciliary body of one horse confirmed the presence of abundant extracellular deposits of non-branching fibrils (9-11 nm in diameter) consistent with amyloid. Immunohistochemistry revealed strong positive labelling for AA amyloid and mass spectrometry showed the amyloid to consist primarily of serum amyloid A1 in both cases. The findings suggest that localized, intraocular AA amyloidosis may occur in horses with ERU., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Equine recurrent uveitis is a severe and frequent blinding disease in horses which presents with auto-reactive invading T-cells, resulting in the destruction of the inner eye. Infiltration of inflammatory cells into the retina and vitreous is driven by currently unknown guidance cues, however surgical removal of the vitreous (vitrectomy) has proven therapeutically successful. Therefore, proteomic analyses of vitrectomy samples are likely to result in detection of proteins contributing to disease pathogenesis. Vitreous from healthy and ERU diseased horses were directly compared by quantitative mass spectrometry based on label-free quantification of peak intensities across samples. We found a significant upregulation of complement and coagulation cascades and downregulation of negative paracrine regulators of canonical Wnt signalling including the Wnt signalling inhibitors DKK3 and SFRP2. Based on immunohistochemistry, both proteins are expressed in equine retina and suggest localisation to retinal Müller glial cells (RMG), which may be the source cells for these proteins. Furthermore, retinal expression levels and patterns of DKK3 change in response to ERU. Since many other regulated proteins identified here are associated with RMG cells, these cells qualify as the prime responders to autoimmune triggers., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The molecular mechanism which enables activated immune cells to cross the blood-retinal barrier in spontaneous autoimmune uveitis is yet to be unraveled. Equine recurrent uveitis is the only spontaneous animal model allowing us to investigate the autoimmune mediated transformation of leukocytes in the course of this sight threatening disease. Hypothesizing that peripheral blood immune cells change their protein expression pattern in spontaneous autoimmune uveitis, we used DIGE to detect proteins with altered abundance comparing peripheral immune cells of healthy and ERU diseased horses. Among others, we found a significant downregulation of talin 1 in peripheral blood granulocytes of ERU specimen, pointing to changes in β integrin activation and indicating a significant role of the innate immune system in spontaneous autoimmune diseases., (Copyright © 2012. Published by Elsevier B.V.)

A male Jack Russell terrier developed bilateral uveitis and glaucoma at 1 year of age. Since the ocular disease was painful and unresponsive to treatment, both globes were enucleated. Microscopical evaluation of one enucleated globe revealed panuveitis, with pigment dispersion and phagocytosis consistent with the ocular lesions of canine Vogt-Koyanagi-Harada (VKH)-like syndrome. Three years later the dog was represented with severe muscle disease and skin lesions. Due to rapid clinical deterioration the dog was humanely destroyed. Necropsy examination revealed lichenoid interface inflammation in the skin and mucous membranes, with pigmentary incontinence consistent with VKH-like syndrome and lymphocytic and histiocytic polymyositis with marked muscle atrophy. Canine VKH-like syndrome is an autoimmune disease that targets melanocyte antigens. Some human patients with VKH disease develop additional autoimmune diseases. To our knowledge this is the first reported case of polymyositis subsequent to VKH-like disease in a dog. In addition, VKH-like disease has not been previously reported in a Jack Russell terrier., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Anti-Toxoplasma gondii antibodies were determined in serum and aqueous humor of two groups of cats in France: cats with uveitis (group 1, n=26) and cats with systemic disease (group 2, n=24) using an agglutination test. Titres above 1:64 were considered positive. IgG antibodies to T. gondii were detected in 10 serum samples from group 1 and in 10 serum samples from group 2, and in 2 aqueous humor samples from group 1 and in 1 aqueous humor samples from group 2. The distribution of ocular lesions according to the serological status of the animals indicated that lens luxation and buphthalmia were more frequent in T. gondii seropositive cats than in seronegative ones. The study reports a similar prevalence of anti-T. gondii antibodies in cats with uveitis and in cats without uveitis in France. Serological results must be analysed carefully and additional diagnostic tools is required.

The purpose of this study was to determine the temporal appearance of T. gondii in aqueous humor of cats orally inoculated with T. gondii using polymerase chain reaction (PCR) for the detection of the B1 gene. Serum and aqueous humor were collected from five SPF cats prior to oral inoculation with T. gondii and days 7, 14, 21, 28, 42, 84, 140, 147, 154, 161, 168, and 182 after inoculation. Cats were inoculated orally with T. gondii tissue cysts on day 0 and day 140. T. gondii-specific IgM and IgG were measured in serum and aqueous humor from the cats at each sample data. T. gondii B1 gene PCR was performed on all the aqueous humor samples and the amplified DNA was detected by Southern blotting. Chorioretinitis developed in three out of the five cats, but anterior uveitis was not detected. All cats developed T. gondii-specific IgG titers in serum, and had T. gondii-specific IgG C-values > 1 in both eyes at varying times during the study. T. gondii was detected by PCR and Southern blotting in aqueous humor in both eyes of all cats at times varying from days 14-84 after primary inoculation and days 14-42 after challenge inoculation.