Proteomic insight into the pathogenesis of CAPN5-vitreoretinopathy

Gabriel Velez; Jing Yang; Angela S Li; Stephen H Tsang; Alexander G Bassuk; Vinit B Mahajan

doi:10.1038/s41598-019-44031-7

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Proteomic insight into the pathogenesis of CAPN5-vitreoretinopathy

Journal article

Open access

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Proteomic insight into the pathogenesis of CAPN5-vitreoretinopathy

Gabriel Velez, Jing Yang, Angela S Li, Stephen H Tsang, Alexander G Bassuk and Vinit B Mahajan

Scientific reports, Vol.9(1), pp.7608-7608

05/20/2019

DOI: 10.1038/s41598-019-44031-7

PMCID: PMC6527583

PMID: 31110225

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Abstract

CAPN5 Neovascular Inflammatory Vitreoretinopathy (CAPN5-NIV; OMIM 193235) is a poorly-understood rare, progressive inflammatory intraocular disease with limited therapeutic options. To profile disease effector proteins in CAPN5-NIV patient vitreous, liquid vitreous biopsies were collected from two groups: eyes from control subjects (n = 4) with idiopathic macular holes (IMH) and eyes from test subjects (n = 12) with different stages of CAPN5-NIV. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein expression changes were evaluated by principal component analysis, 1-way ANOVA (significant p-value < 0.05), hierarchical clustering, gene ontology, and pathway representation. There were 216 differentially-expressed proteins (between CAPN5-NIV and control vitreous), including those unique to and abundant in each clinical stage. Gene ontology analysis revealed decreased synaptic signaling proteins in CAPN5-NIV vitreous compared to controls. Pathway analysis revealed that inflammatory mediators of the acute phase response and the complement cascade were highly-represented. The CAPN5-NIV vitreous proteome displayed characteristic enrichment of proteins and pathways previously-associated with non-infectious posterior uveitis, rhegmatogenous retinal detachment (RRD), age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR), and proliferative vitreoretinopathy (PVR). This study expands our knowledge of affected molecular pathways in CAPN5-NIV using unbiased, shotgun proteomic analysis rather than targeted detection platforms. The high-levels and representation of acute phase response proteins suggests a functional role for the innate immune system in CAPN5-NIV pathogenesis.

Biomarkers

Eye diseases

Proteomics

Details

Title: Subtitle: Proteomic insight into the pathogenesis of CAPN5-vitreoretinopathy
Creators: Gabriel Velez - Palo Alto, CA USA
Jing Yang - Palo Alto, CA USA
Angela S Li - Palo Alto, CA USA
Stephen H Tsang - New York, NY USA
Alexander G Bassuk - Iowa City, IA USA
Vinit B Mahajan - Palo Alto, CA USA
Resource Type: Journal article
Publication Details: Scientific reports, Vol.9(1), pp.7608-7608
DOI: 10.1038/s41598-019-44031-7
PMID: 31110225
PMCID: PMC6527583
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: Nature Publishing Group UK; London
Grant note: ; 2013103 / ; F30EYE027986 / ; 5P30CA013696 / ; T32GM007337; 5P30EY019007, R01EY018213, R01EY024698, R01EY026682, R21AG050437; K08EY020530, R01EY024665, R01EY025225, R01EY024698, R21AG050437, P30EY026877; K08EY020530, R01EY024665, R01EY025225, R01EY024698, R21AG050437, P30EY026877 / ;
Language: English
Date published: 05/20/2019
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984070678602771

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