Abstract
PurposeHuman vitreoretinal diseases are due to presumed abnormal mechanical interactions between the vitreous and retina, and translational models are limited. This study determined whether nonstructural proteins and potential retinal biomarkers were expressed by the normal mouse vitreous and retina. MethodsVitreous and retina samples from mice were collected by evisceration and analyzed by liquid chromatography-tandem mass spectrometry. Identified proteins were further analyzed for differential expression and functional interactions using bioinformatic software. ResultsWe identified 1,680 unique proteins in the retina and 675 unique proteins in the vitreous. Unbiased clustering identified protein pathways that distinguish retina from vitreous including oxidative phosphorylation and neurofilament cytoskeletal remodeling, whereas the vitreous expressed oxidative stress and innate immunology pathways. Some intracellular protein pathways were found in both retina and vitreous, such as glycolysis and gluconeogenesis and neuronal signaling, suggesting proteins might be shuttled between the retina and vitreous. We also identified human disease biomarkers represented in the mouse vitreous and retina, including carbonic anhydrase-2 and 3, crystallins, macrophage inhibitory factor, glutathione peroxidase, peroxiredoxins, S100 precursors, and von Willebrand factor. ConclusionsOur analysis suggests the vitreous expresses nonstructural proteins that functionally interact with the retina to manage oxidative stress, immune reactions, and intracellular proteins may be exchanged between the retina and vitreous. This novel proteomic dataset can be used for investigating human vitreoretinopathies in mouse models. Validation of vitreoretinal biomarkers for human ocular diseases will provide a critical tool for diagnostics and an avenue for therapeutics.
Highlights
Vitreoretinal diseases encompass blinding conditions due to abnormal interactions between the inner surface of the neurosensory retina and the overlying vitreous gel
Serum ELISA assays have been developed as cancer diagnostic tests, such as those for MUC5AC and NPC-1C to identify tumor growth in colorectal and pancreatic cancers or C-erbB-2 in breast cancer[8,9]
The success of anti-vascular endothelial growth factor (VEGF) therapy in vein occlusions and diabetic retinopathy supports the search for biomarkers in other vitreoretinal diseases
Summary
Vitreoretinal diseases encompass blinding conditions due to abnormal interactions between the inner surface of the neurosensory retina and the overlying vitreous gel. An ELISA of specific vitreous proteins could be used for disease diagnostics. Serum ELISA assays have been developed as cancer diagnostic tests, such as those for MUC5AC and NPC-1C to identify tumor growth in colorectal and pancreatic cancers or C-erbB-2 in breast cancer[8,9]. Retinal proteins, such as vascular endothelial growth factor (VEGF), can be detected in the vitreous of angiogenic vitreoretinopathies using an ELISA assay. The success of anti-VEGF therapy in vein occlusions and diabetic retinopathy supports the search for biomarkers in other vitreoretinal diseases
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