Format

Send to

Choose Destination
Sci Rep. 2019 May 20;9(1):7608. doi: 10.1038/s41598-019-44031-7.

Proteomic insight into the pathogenesis of CAPN5-vitreoretinopathy.

Velez G1,2,3, Yang J1,2, Li AS1,2, Tsang SH4,5, Bassuk AG6, Mahajan VB7,8,9.

Author information

1
Omics Laboratory, Stanford University, Palo Alto, CA, USA.
2
Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USA.
3
Medical Scientist Training Program, University of Iowa, Iowa City, IA, USA.
4
Jonas Children's Vision Care, and Bernard & Shirlee Brown Glaucoma Laboratory, Columbia Stem Cell Initiative, Departments of Ophthalmology, Pathology & Cell Biology, Institute of Human Nutrition, Columbia University, New York, NY, USA.
5
Department of Pathology & Cell Biology, College of Physicians & Surgeons, Columbia University, New York, NY, USA.
6
Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
7
Omics Laboratory, Stanford University, Palo Alto, CA, USA. vinit.mahajan@stanford.edu.
8
Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USA. vinit.mahajan@stanford.edu.
9
Palo Alto Veterans Administration, Palo Alto, CA, USA. vinit.mahajan@stanford.edu.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center