@article {677, title = {Precision Medicine: Personalized Proteomics for the Diagnosis and Treatment of Idiopathic Inflammatory Disease.}, journal = {JAMA Ophthalmol}, volume = {134}, year = {2016}, month = {2016 Apr}, pages = {444-8}, abstract = {

IMPORTANCE: To better characterize posterior uveitis, vitreous samples from 15 patients were subjected to antibody arrays, and the expression levels of 200 human cytokines were evaluated. Expression was analyzed by 1-way analysis of variance (significance at P < .01), unsupervised cluster algorithm, and pathway analysis.

OBSERVATIONS: Unbiased clustering of patients, based on their cytokine expression profile, suggested that particular protein networks and molecular pathways are altered in various forms of uveitis. Expression of interleukin 23 (IL-23), IL-1 receptor I (IL-1RI), IL-17R, tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2), insulinlike growth factor-binding protein 2 (IGFBP-2), nerve growth factor (b-NGF), platelet-derived growth factor receptor β polypeptide (PDGFRb), bone morphogenic protein 4 (BMP-4), and stem cell factor (SCF) constituted a common cytokine signature in the vitreous of patients with uveitis. In 1 patient with progressive, idiopathic visual loss, this last-line analysis implicated retinal autoimmunity, a diagnosis that was validated when her serum sample was found to contain antibodies to S-arrestin, a retinal protein and potent cause of autoimmune retinal degeneration.

CONCLUSIONS AND RELEVANCE: The analysis identifies a common cytokine signature for posterior uveitis and guides the diagnosis of a patient with idiopathic uveitis. Personalized treatment reversed the visual loss, illustrating how proteomic tools may individualize therapy.

}, keywords = {Adrenal Cortex Hormones, Adult, Analysis of Variance, Case-Control Studies, Cytokines, Follow-Up Studies, Humans, Immunosuppressive Agents, Male, Middle Aged, Precision Medicine, Proteomics, Reference Values, Risk Assessment, Severity of Illness Index, Treatment Outcome, Uveitis, Visual Acuity}, issn = {2168-6173}, doi = {10.1001/jamaophthalmol.2015.5934}, author = {Velez, Gabriel and Roybal, C Nathaniel and Colgan, Diana and Tsang, Stephen H and Bassuk, Alexander G and Mahajan, Vinit B} } @article {699, title = {Structural modeling of a novel CAPN5 mutation that causes uveitis and neovascular retinal detachment.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0122352}, abstract = {

CAPN5 mutations have been linked to autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a blinding autoimmune eye disease. Here, we link a new CAPN5 mutation to ADNIV and model the three-dimensional structure of the resulting mutant protein. In our study, a kindred with inflammatory vitreoretinopathy was evaluated by clinical eye examinations, DNA sequencing, and protein structural modeling to investigate the disease-causing mutation. Two daughters of an affected mother demonstrated symptoms of stage III ADNIV, with posterior uveitis, cystoid macular edema, intraocular fibrosis, retinal neovascularization, retinal degeneration, and cataract. The women also harbored a novel guanine to thymine (c.750G\>T, p.Lys250Asn) missense mutation in exon 6 of CAPN5, a gene that encodes a calcium-activated cysteine protease, calpain-5. Modeling based on the structures of all known calpains revealed the mutation falls within a calcium-sensitive flexible gating loop that controls access to the catalytic groove. Three-dimensional modeling placed the new mutation in a region adjacent to two previously identified disease-causing mutations, all three of which likely disrupt hydrogen bonding within the gating loop, yielding a CAPN5 with altered enzymatic activity. This is the third case of a CAPN5 mutation leading to inherited uveitis and neovascular vitreoretinopathy, suggesting patients with ADNIV features should be tested for CAPN5 mutations. Structural modeling of novel variants can be used to support mechanistic consequences of the disease-causing variants.

}, keywords = {Base Sequence, Calpain, Computational Biology, DNA Primers, Female, Fluorescein Angiography, Humans, Models, Molecular, Molecular Sequence Data, Mutation, Missense, Pedigree, Phenotype, Protein Conformation, Retinal Detachment, Sequence Analysis, DNA, Tomography, Optical Coherence, Uveitis, Vitreoretinopathy, Proliferative}, issn = {1932-6203}, doi = {10.1371/journal.pone.0122352}, author = {Bassuk, Alexander G and Yeh, Steven and Wu, Shu and Martin, Daniel F and Tsang, Stephen H and Gakhar, Lokesh and Mahajan, Vinit B} } @article {161, title = {Intravitreal bevacizumab during pregnancy.}, journal = {Retina (Philadelphia, Pa.)}, volume = {30}, year = {2010}, month = {2010 Oct}, pages = {1405-11}, abstract = {

To report the clinical course of four women treated with intravitreal bevacizumab during pregnancy.

}, keywords = {Adult, Angiogenesis Inhibitors, Antibodies, Monoclonal, Choroidal Neovascularization, Eye Infections, Fungal, Female, Follow-Up Studies, Gestational Age, Histoplasmosis, Humans, Intravitreal Injections, Off-Label Use, Pregnancy, Pregnancy Complications, Sarcoidosis, Tomography, Optical Coherence, Uveitis, Vascular Endothelial Growth Factor A, Visual Acuity}, author = {Tarantola, Ryan M and Folk, James C and Boldt, H Culver and Mahajan, Vinit B} }