However, when considering the closest vascularized tissuethe uvea, an increase in inflammatory cells is noted, especially in the ciliary body [93,94], but also within the vitreous cavity [47,48,53,95]

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However, when considering the closest vascularized tissuethe uvea, an increase in inflammatory cells is noted, especially in the ciliary body [93,94], but also within the vitreous cavity [47,48,53,95]. microcolonies and dense roundish accumulations of spp. In many instances spirochetes were surrounded by an extracellular substance. Taken together, data from the present study show that ERU is a biofilm-associated intraocular leptospiral infection, which best explains the typical clinical course. spp., immune tolerance, antibiotic tolerance, equine recurrent uveitis (ERU), vitreous humor, immunohistochemistry, Warthin-Starry silver stain 1. Introduction Biofilm-associated infections are characterized by persistent (-)-Licarin B and progressive disease in which the inflammatory response surrounding the biofilm plays a significant role [1,2]. Four steps of biofilm formation have been explained: (1) solitary bacteria; (2) the formation of microcolonies; (3) a mature biofilm; and (4) the separation of biofilm and launch of planktonic bacteria [3]. In vitro biofilm formation has been explained in detail for spp. [4,5,6] and there is evidence of in vivo MAP3K11 biofilm formation following experimental infections [7,8]. In horses, recurrent uveitis happens at unpredictable intervals over a period of many years and usually prospects to blindness despite rigorous traditional therapy [9,10,11]. Both eyes are affected in about 25C50% of horses [12,13]. ERU affects up to 10% of all horses in Europe [14,15,16] and up to 25% in the US [17]. In Western horses without a leopard coating pattern, the most effective method to prevent further episodes of uveitis and therefore preserve vision is definitely vitrectomy [10,18,19,20,21]. After a properly performed vitrectomy, which has been regularly performed for more than 30 years in horses with ERU, the control of swelling is seen in 90C97% of horses [10,13,21,22,23,24]. By contrast, uveitis in horses having a leopard coating pattern manifests in a different way. Affected horses typically do not look like as painful. Intraocular leptospiral illness is rarely confirmed suggesting the etiology and (-)-Licarin B pathogenesis are different from that seen in horses without a leopard coating pattern [25]. The vitreous eliminated during vitrectomy are intensely investigated in the hope of better determining etiology, pathogenesis and treatment strategies for ERU. Many of these studies possess suggested an association between leptospiral illness and ERU [26,27,28,29,30,31]. For example, anti-antibodies are regularly recognized in vitreous material acquired during vitrectomies [13,15,21,32,33,34,35,36,37,38,39,40,41]. These antibodies are recognized using the micro agglutination test (MAT), and various enzyme-linked immunosorbent assays (ELISA) [42,43]. In additional studies, spp. are cultured and anti-antibodies are recognized in the same vitreous samples [13,21,32,35,39,44,45,46]. In addition, gene or 16S-rRNA are recognized by a polymerase chain reaction (PCR) in up to 70% of intraocular samples collected from affected horses [32,39,43,44,45]. Finally, scanning electron microscopy is used to reliably detect spp. in vitreous material from equine eyes affected with recurrent uveitis. The leptospiral organisms were surrounded by a homogeneous granular coating, which has not been seen in spp. cultured in vitro (using standard World Health Business (WHO) strains) [47,48]. In addition to direct evidence of the leptospiral illness of vitreous samples from eyes affected with ERU, evidence of autoimmunity also is present [49]. However, Prof. Deegs study group [50] performed all investigations using vitreous samples, from which leptospiral infections were also regularly recognized [13,21,39,41,42,43,46]. Furthermore, while vitrectomy removes the vitreous material, potential autoantigens from additional tissuesespecially the lens and retinaremain in the eye [18,39] which contradicts the idea of autoimmunity [39,51]. Taken collectively, data from several studies using specimens from eyes affected with ERU support the hypothesis that ERU is definitely induced and perpetuated from the chronic illness of the vitreous cavity with spp., and that this may be eliminated by vitrectomy [13,21,32,33,36,37,39,44]. However, systemic antibiotic therapy has not been successful at controlling the inflammation seen in ERU. The vitreous body consists of 98C99% water, consists of collagen fibrils and represents a 28 mL immunological market in horses [13,39,52,53,54]. These are ideal conditions for the biofilm production of the spp. [55]. In addition, ERU exhibits (-)-Licarin B all the characteristics of a biofilm illness: chronicity, swelling, and a high tolerance to both antibiotics [46] and the bodys immune defenses. The aim of this ex vivo study was to demonstrate,.