Abstract
The blockbuster drug paradigm is under increasing scrutiny across the biopharmaceutical industry. Intraocular inflammation poses particular challenges to this, given the heterogeneity of conditions in the uveitis spectrum, and the increasing acknowledgement of individual patient and disease variance in underlying immune responses. This need has triggered a drive towards personalised and stratified medicine, supported and enabled as a result of continued development of both experimental models and molecular biological techniques and improved clinical classification. As such we have the ability now to systematically appraise at a genomic, transcriptomic, and proteomic level individual immunophenotype, and the promise that in the eye this can be augmented by in vivo immune imaging to identify individual immunopathology. With such advances all running in parallel, we are entering an era of experimental medicine that will facilitate early diagnosis, generate biomarkers for accurate prognostication, and enable the development of individualised and targeted therapies, which can progress rapidly into clinical practice.
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Acknowledgements
RWL is funded as a clinical lecturer by the NIHR and both ADD and RWL are faculty of the NIHR Biomedical Research Centre for Ophthalmology (Moorfields Eye Hospital and UCL Institute of Ophthalmology). The review was in part supported by grants from the National Eye Research Centre, Dunhill Medical Foundation, and Underwood Trust.
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Appendix
Appendix
Caspase-1
One of the cysteine proteases family is involved in cleaving IL-1β and is activated in the inflammasome and contributes to inflammasome activation and generation of pro-inflammatory state.
Pyrin
Pyrin is a protein produced by white blood cells (neutrophils, eosinophils, and macrophages) encoded by MEFV (Mediterranean Fever) and various pathogen recognition receptors (PPRs) have pyrin-binding domains.
NOD
Nucleotide oligomerization domain. There are several genes encoding for NOD and NOD2 gene (nucleotide-binding oligomerization domain containing 2) encodes for a protein, NOD2, also known as the caspase recruitment domain family, member 15 (CARD15), and an intracellular PPR. Other NLR proteins include NALPs and NAIP.
NALPs
NACHT (neuronal apoptosis inhibitory protein (NAIP), MHC class II transcription activator (CIITA), incompatibility locus protein from Podospora anserine (HET-E), and telomerase-associated protein (TP1)), leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein; a member of the nucleotide-binding oligomerization domain NLR family of intracellular proteins that sense components of pathogens and dying cells.
NAIP
Neuronal apoptosis inhibitory protein.
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Lee, R., Dick, A. Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation. Eye 26, 17–28 (2012). https://doi.org/10.1038/eye.2011.255
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DOI: https://doi.org/10.1038/eye.2011.255
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