June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Vitreous Proteome profile of proliferative diabetic retinopathy (PDR) and idiopathic macular hole (IMH): a comparative analysis
Author Affiliations & Notes
  • Sagnik Sen
    Vitreo-retina, Aravind Eye Hospital, Madurai, India
    Proteomics, Aravind Medical Research Foundation, Madurai, India
  • Dharmalingam K
    Proteomics, Aravind Medical Research Foundation, Madurai, India
  • Naresh Babu K
    Vitreo-retina, Aravind Eye Hospital, Madurai, India
  • Jeya Maheshwari
    Vitreo-retina, Aravind Eye Hospital, Madurai, India
  • Kim Ramasamy
    Vitreo-retina, Aravind Eye Hospital, Madurai, India
  • Footnotes
    Commercial Relationships   Sagnik Sen, None; Dharmalingam K, None; Naresh K, None; Jeya Maheshwari, None; Kim Ramasamy, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 5006. doi:
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      Sagnik Sen, Dharmalingam K, Naresh Babu K, Jeya Maheshwari, Kim Ramasamy; Vitreous Proteome profile of proliferative diabetic retinopathy (PDR) and idiopathic macular hole (IMH): a comparative analysis. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5006.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Several pathways have been proposed to explain the pathogenesis of diabetic retinopathy. In this study we examined proteins representing known and new pathways responsible for PDR by comparing vitreous proteome of PDR and IMH.

Methods : Undiluted vitreous samples were collected from patients undergoing vitrectomy for PDR (9) and IMH (10). Pooled samples were fractionated using 1-D SDS gel electrophoresis and stained with Coomassie-blue. Gel separated proteins were processed for liquid chromatography-mass spectrometry as described previously. Proteome discoverer software was used for protein identification. Annotation of protein related diseases, biological processes, cellular components and molecular functions was performed via DAVID bioinformatics tool.

Results : PDR and IMH vitreous proteome share 113 proteins and the rest were unique to the conditions examined. Figure 1 shows Gene ontology analysis. Upregulated proteins in PDR were Carbonic anhydrase 1, Cystatin-C, Alpha 1 antichymotrypsin, Afamin, Vitronectin, Protein S100A8, Hemopexin and Histidine-rich glycoprotein. Downregulated in PDR were Pigment epithelium-derived factor (PEDF), Alpha-1-antitrypsin, Lipophilin B, Glutathione peroxidase, Cathepsin D, Lipocalin-1, Alpha-1-acid glycoprotein 1, Prostaglandin-H2 D-isomerase and Gasdermin. PDR vitreous showed unique presence of Clusterin, Fibronectin, Apolipoproteins AIV, AII, B100, C1s, C3, alpha-2-HS-glycoprotein and BAX; and absence of antithrombin-III, neuroserpin, sialidase, GFAP and myocilin.

Conclusions : PDR proteome had increased function in protease inhibition, inflammation, metabolic syndrome, cytoskeleton modulation, coagulation and fibrinolysis cascades and reduced function in antiangiogenesis, neuroinflammation inhibition, antioxidant activity, photoreceptor regeneration, adherens junction, anti-inflammatory activity and platelet aggregation. These pathways may need further analyses to obtain a clearer composite picture of diabetic retinopathy pathogenesis.

This is a 2020 ARVO Annual Meeting abstract.

 

Figure 1: Gene Ontology showing more than 5% proteins abundant in PDR and IMH groups. (A) Biological processes, (B) cellular components, (C) Molecular functions, (D) Disease classifications. PDR vitreous showed enrichment in several novel pathways.

Figure 1: Gene Ontology showing more than 5% proteins abundant in PDR and IMH groups. (A) Biological processes, (B) cellular components, (C) Molecular functions, (D) Disease classifications. PDR vitreous showed enrichment in several novel pathways.

 

Figure 2: 18 proteins upregulated and 17 downregulated in PDR vitreous. Maximum downregulation seen in PEDF and Alpha-1-antitrypsin.

Figure 2: 18 proteins upregulated and 17 downregulated in PDR vitreous. Maximum downregulation seen in PEDF and Alpha-1-antitrypsin.

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