Eyeworld

75 EW INTERNATIONAL December 2016 leasing peptides that selectively bind to the B27 molecule. The B27 mol- ecule then presents as an antigen to T cells, which will generate an immunologic response, leading to uveitis. These cells will also secrete cytokines like the IL-23, which affect T cells and lead to uveitis. This has implications for the therapy of this disease because we can now attack the disease on a number of different levels." Still, some aspects of AAU defy explanation, such as disease local- ization in the anterior uvea, the cause of recurrent disease, the roles of innate and acquired immune responses, preventing attacks and complications, the role of genet- ics, and so on. Currently, the use of corticosteroids and cycloplegics effectively treats 90% of AAU cases. Research over the past decade has provided decisive evidence to act on for planning future research and for taking on AAU from different angles, such as blocking the inflammatory cytokine pathway and the B27 mol- ecule-stimulatory pathway, among others. Although still hypothetical, the pathophysiological pathway gives physicians a structure to un- derstand AAU and the role of genes and pro-inflammatory cytokines in its pathogenesis. EW References 1.Wakefield D, et al. What is new HLA-B27 acute anterior uveitis? Ocul Immunol Inflamm. 2011;19:139–144. 2. Robinson PC, et al. Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis. Arthritis Rheumatol. 2015;67:140–151. 3. Schittenhelm RC, et al. Revisiting the arthritogenic peptide theory: quantitative not qualitative changes in the peptide repertoire of HLA-B27 allotypes. Arthritis Rheumatol. 2015;67:702–13. 4. Mai K, et al. Role of toll-like receptors in human iris pigment epithelial cells and their response to pathogen-associated molecular patterns. J Inflamm (Lond). 2014;11:20. Editors' note: Dr. Wakefield has no financial interests related to his comments. Contact information Wakefield: d.wakefield@unsw.edu.au identified, contributing evidence of the ever-growing number of poten- tial antigens. Microbial triggers have been suggested in HLA-B27-associated AAU. A large number of studies have indicated a microbial association with organisms such as Chlamydia trachomatis, Yersinia enterocolitica, Salmonella and Shigella species, Klebsiella pneumoniae, Campylobacter jejuni, Helicobacter pylori, Coxiella bur- netii, and microbiomes. Studies have investigated the clinical association between AAU and microbes, serolo- gy, T cell reactivity, HLA-B27 bind- ing peptides, and animal models. The molecular mechanisms responsible for the tissue-specific inflammation in the anterior uvea are incompletely understood. Im- plicated are toll-like receptors (TLR), cytokine production, cross reactive immune response molecular mimic- ry, and T cells. TLR are important innate im- mune receptors expressed on human iris and retinal pigment epithelial cells (IPE and RPE), which, when activated, also may contribute to inflammatory eye diseases such as uveitis. According to the outcomes of one study, the ocular pigment epithelial cells responded to patho- gen-associated molecular patterns (PAMPs) through activation of TLRs, particularly to TLR1/2, TLR3, TLR4, and TLR2/6 agonists. 4 The study showed a high secretion of cytokine in lipopolysaccharide-stimulated hu- man IPE cells. Overall, the evidence indicated that human IPE cells in culture were more sensitive than RPE cells to PAMPs. Putting it together Putting all of these new facts and findings together requires some skill. Dr. Wakefield explained, "The pathogenesis of AAU seems to look as follows: An initial stimulus in the form of a microbial infection or from the microbiome activates TLRs, which appear crucial in initiating this response in the uveal cells. Animal models suggest that microor- ganisms cause PAMPS to be released, which cause TLR activation. Mi- crobes may also be phagocytosed by phagocytic cells in the anterior uvea, where they are then processed, re- Maastricht2017 21 ST ESCRS WINTER MEETING 10 –12 February In conjunction with the Netherlands Intra Ocular Implant Club & the Belgian Society of Cataract & Refractive Surgery The Netherlands Preliminary Programme, Registration & Hotel Bookings Available Online www.escrs.org At the MECC Maastricht

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