Journal article
Personalized Proteomics in Proliferative Vitreoretinopathy Implicate Hematopoietic Cell Recruitment and mTOR as a Therapeutic Target
American journal of ophthalmology, Vol.186, pp.152-163
02/2018
DOI: 10.1016/j.ajo.2017.11.025
PMCID: PMC5805631
PMID: 29246578
Abstract
To profile vitreous cytokine expression of proliferative vitreoretinopathy (PVR) patients.\nCase-control study.\nLiquid biopsies were collected from 2 groups: control subjects (n = 3) undergoing pars plana vitrectomy to remove an epiretinal membrane (ERM), and test subjects (n = 7) with varying degrees of PVR. A high-throughput cytokine screen measured expression of 200 cytokines. Cytokine expression patterns were prospectively validated in separate cohorts of control patients and those with PVR-A, PVR-B, and PVR-C (n = 10 for each group). Expression changes were evaluated by analysis of variance (significant P value < .05), hierarchical cluster algorithm, and pathway analysis, to identify candidate pathways for prospective studies.\nIn PVR vitreous, 29 cytokines were upregulated compared to controls. Early PVR vitreous showed upregulation of T-cell markers, profibrotic cytokines, and cytokines downstream of mTOR activation (IL-2, IL-6, and IL-13), whereas in late PVR vitreous, cytokines driving monocyte responses and stem-cell recruitment (SDF-1) prevailed. Prospective validation confirmed the differential expression of specific cytokines from PVR-A to C.\nEarly PVR is characterized by activation of T cells and mTOR signaling, whereas advanced PVR is characterized by a chronic monocyte response. PVR might be treated by rational repositioning of existing drugs that target mTOR and IL-6. Our analysis demonstrates that successful therapeutic intervention will be highly dependent on the specific therapeutic target and the stage of PVR. This study provides insights into cytokines that will serve as biomarkers and therapeutic targets. These biomarkers will help design clinical trials that intervene at appropriate times.
Details
- Title: Subtitle
- Personalized Proteomics in Proliferative Vitreoretinopathy Implicate Hematopoietic Cell Recruitment and mTOR as a Therapeutic Target
- Creators
- C Nathaniel Roybal - Eye Associates of New Mexico, Albuquerque, New Mexico; Department of Surgery, University of New Mexico, Albuquerque, New Mexico; Omics Laboratory, Stanford University, Palo Alto, CaliforniaGabriel Velez - Omics Laboratory, Stanford University, Palo Alto, California; Medical Scientist Training Program, University of Iowa, Iowa City, IowaMarcus A Toral - Omics Laboratory, Stanford University, Palo Alto, California; Medical Scientist Training Program, University of Iowa, Iowa City, IowaStephen H Tsang - Barbara and Donald Jonas Laboratory of Stem Cells and Regenerative Medicine and Bernard & Shirlee Brown Glaucoma Laboratory, Edward S. Harkness Eye Institute, Columbia University, New York, New York; Department of Pathology & Cell Biology, College of Physicians & Surgeons, Columbia University, New York, New YorkAlexander G Bassuk - Department of Pediatrics, University of Iowa, Iowa City, IowaVinit B Mahajan - Omics Laboratory, Stanford University, Palo Alto, California; Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, California; Palo Alto Veterans Administration, Palo Alto, California. Electronic address: vinit.mahajan@stanford.edu
- Resource Type
- Journal article
- Publication Details
- American journal of ophthalmology, Vol.186, pp.152-163
- DOI
- 10.1016/j.ajo.2017.11.025
- PMID
- 29246578
- PMCID
- PMC5805631
- NLM abbreviation
- Am J Ophthalmol
- ISSN
- 0002-9394
- eISSN
- 1879-1891
- Publisher
- United States
- Grant note
- R01 EY025225 / NEI NIH HHS\nR01 EY018213 / NEI NIH HHS\nP30 CA013696 / NCI NIH HHS\nR01 EY024698 / NEI NIH HHS\nT32 GM007337 / NIGMS NIH HHS\nR01 EY026682 / NEI NIH HHS\nK08 EY020530 / NEI NIH HHS\nR01 EY024665 / NEI NIH HHS\nR21 AG050437 / NIA NIH HHS\nP30 EY019007 / NEI NIH HHS
- Language
- English
- Date published
- 02/2018
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984070383502771
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