Proteomic Insight into the Molecular Function of the Vitreous
Open accessAbstract
The human vitreous contains primarily water, but also contains proteins which have yet to be fully characterized. To gain insight into the four vitreous substructures and their potential functions, we isolated and analyzed the vitreous protein profiles of three non-diseased human eyes. The four analyzed substructures were the anterior hyaloid, the vitreous cortex, the vitreous core, and the vitreous base. Proteins were separated by multidimensional liquid chromatography and identified by tandem mass spectrometry. Bioinformatics tools then extracted the expression profiles, signaling pathways, and interactomes unique to each tissue. From each substructure, a mean of 2,062 unique proteins were identified, with many being differentially expressed in a specific substructure: 278 proteins were unique to the anterior hyaloid, 322 to the vitreous cortex, 128 to the vitreous base, and 136 to the vitreous core. When the identified proteins were organized according to relevant functional pathways and networks, key patterns appeared. The blood coagulation pathway and extracellular matrix turnover networks were highly represented. Oxidative stress regulation and energy metabolism proteins were distributed throughout the vitreous. Immune functions were represented by high levels of immunoglobulin, the complement pathway, damage-associated molecular patterns (DAMPs), and evolutionarily conserved antimicrobial proteins. The majority of vitreous proteins detected were intracellular proteins, some of which originate from the retina, including rhodopsin (RHO), phosphodiesterase 6 (PDE6), and glial fibrillary acidic protein (GFAP). This comprehensive analysis uncovers a picture of the vitreous as a biologically active tissue, where proteins localize to distinct substructures to protect the intraocular tissues from infection, oxidative stress, and energy disequilibrium. It also reveals the retina as a potential source of inflammatory mediators. The vitreous proteome catalogues the dynamic interactions between the vitreous and surrounding tissues. It therefore could be an indirect and effective method for surveying vitreoretinal disease for specific biomarkers.
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Ocular tissues, including the retina, shed intracellular proteins into adjacent intraocular fluid compartments such as vitreous fluid.
“proteomic studies of the eye reveal that ocular tissues, including the retina, shed intracellular proteins into adjacent intraocular fluid compartments (e.g., the vitreous fluid; Fig. 1a)20,26–28.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [20]
The eye lacks T-cells but contains antibodies, cytokines, and resident immune cells.
“While the eye lacks T-cells, it contains antibodies, cytokines, and resident immune cells.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [20]
Vitreous fluid makes up 80% of the human eye by volume.
“This tissue makes up 80% of the human eye by volume and sequesters both intracellular and extracellular proteins shed from the retina and adjacent tissues20,26–28.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [20]
Vitreous fluid biopsies exhibit high enough intracellular and extracellular protein content to serve as proxy biopsies for the retina.
“Biopsies of vitreous fluid exhibit high enough intracellular and extracellular protein content to serve as proxy biopsies for the retina and guide treatment of human disease20,26.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [20]
Vitreous fluid sequesters both intracellular and extracellular proteins shed from the retina and adjacent tissues.
“This tissue makes up 80% of the human eye by volume and sequesters both intracellular and extracellular proteins shed from the retina and adjacent tissues20,26–28.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [20]
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- Authors
- Skeie, J. M., Roybal, C. N., & Mahajan, V. B.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Mahajan, Vinit B.
- ORCID
- Mahajan, Vinit B.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-05-28
- Volume
- 10
- Issue
- 5
- Pages
- e0127567
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4447289
- OpenAlex
- W385732249
- Cited by
- 93
- References
- 59
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 4 · 2023: 8 · 2022: 7 · 2021: 9 · 2020: 20 · 2019: 7 · 2018: 14 · 2017: 10 · 2016: 2 · 2015: 2
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Doris Duke Charitable Foundation (#2013103)
- Research to Prevent Blindness
- National Institutes of Health
- National Eye Institute (R01EY024665, K08EY020530)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal and Macular Surgery
- Keywords
- vitreous proteome, vitreous cortex, vitreous base, extracellular matrix turnover, oxidative stress, energy metabolism, complement pathway, damage-associated molecular patterns, antimicrobial proteins, immunoglobulins, rhodopsin, phosphodiesterase 6, glial fibrillary acidic protein
- MeSH terms
- Aged, Aged, 80 and over, Eye Proteins, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Vitreous Body, Proteome, Proteomics
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