TY - JOUR
T1 - Proteomic profile of vitreous in patients with tubercular uveitis
AU - Bansal, Reema
AU - Khan, Mohd M.
AU - Dasari, Surendra
AU - Verma, Indu
AU - Goodlett, David R.
AU - Manes, Nathan P.
AU - Nita-Lazar, Aleksandra
AU - Sharma, Surya P.
AU - Kumar, Aman
AU - Singh, Nirbhai
AU - Chakraborti, Anuradha
AU - Gupta, Vishali
AU - Dogra, M. R.
AU - Ram, Jagat
AU - Gupta, Amod
N1 - Funding Information:
We thank the participants for their efforts and time during the study. We are thankful to Brian Hampton (Proteomics Core, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA) for providing the laboratory support and skilful assistance for shotgun proteomics of vitreous fluid samples. We also thank Dr Preeti Boria (India), Dr Ravi Sharma (India), Dr Sumedha Sharma (India), and Prof Shobha Sehgal (India) for their technical assistance, and also to the staff of Advanced Eye Centre Research laboratory. RB is thankful to Fogarty AIDS International Training and Research Program (AITRP) and the New York University of School of Medicine (NYUSoM) and for providing partial financial assistance for travelling to the USA. We are thankful to Prof Madhu Khullar, Prof D Behera, Prof SK Arora, Prof Sunil Sethi, and Dr Amit Arora for critical inputs, and for additional support for making the publication possible. MK was thankful to the Graduate Partnership Program (GPP) of the NIH for the graduate education support and American Association of Pharmaceutical Scientists (AAPS) foundation for a graduate student fellowship. Prof Goodlett (DRG) thanks the International Centre for Cancer Vaccine Science project carried out within the International Research Agendas program of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund ( MAB/2017/03 ) for support. This research was supported in part by the Intramural Research program of NIAID, NIH.
Funding Information:
We thank the participants for their efforts and time during the study. We are thankful to Brian Hampton (Proteomics Core, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA) for providing the laboratory support and skilful assistance for shotgun proteomics of vitreous fluid samples. We also thank Dr Preeti Boria (India), Dr Ravi Sharma (India), Dr Sumedha Sharma (India), and Prof Shobha Sehgal (India) for their technical assistance, and also to the staff of Advanced Eye Centre Research laboratory. RB is thankful to Fogarty AIDS International Training and Research Program (AITRP) and the New York University of School of Medicine (NYUSoM) and for providing partial financial assistance for travelling to the USA. We are thankful to Prof Madhu Khullar, Prof D Behera, Prof SK Arora, Prof Sunil Sethi, and Dr Amit Arora for critical inputs, and for additional support for making the publication possible. MK was thankful to the Graduate Partnership Program (GPP) of the NIH for the graduate education support and American Association of Pharmaceutical Scientists (AAPS) foundation for a graduate student fellowship. Prof Goodlett (DRG) thanks the International Centre for Cancer Vaccine Science project carried out within the International Research Agendas program of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund (MAB/2017/03) for support. This research was supported in part by the Intramural Research program of NIAID, NIH. RB and DRG thank Prof Mark Shirtliff, In memoriam (1969-2018), in whose laboratory (Department of Microbial Pathogenesis, School of Dentistry, and Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA) this work began.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2021/1
Y1 - 2021/1
N2 - Objective: To elucidate disease-specific host protein profile in vitreous fluid of patients with intraocular inflammation due to tubercular uveitis (TBU). Methods: Vitreous samples from 13 patients with TBU (group A), 7 with non-TBU (group B) and 9 with no uveitis (group C) were analysed by shotgun proteomics using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) were subjected to pathway analysis using WEB-based Gene SeT Analysis Toolkit software. Results: Compared to control groups (B + C combined), group A (TBU) displayed 32 (11 upregulated, 21 downregulated) DEPs, which revealed an upregulation of coagulation cascades, complement and classic pathways, and downregulation of metabolism of carbohydrates, gluconeogenesis, glucose metabolism and glycolysis/gluconeogenesis pathways. When compared to group B (non-TBU) alone, TBU displayed 58 DEPs (21 upregulated, 37 downregulated), with an upregulation of apoptosis, KRAS signaling, diabetes pathways, classic pathways, and downregulation of MTORC1 signaling, glycolysis/gluconeogenesis, and glucose metabolism. Conclusion: This differential protein profile provides novel insights into the molecular mechanisms of TBU and a baseline to explore vitreous biomarkers to differentiate TBU from non-TBU, warranting future studies to identify and validate them as a diagnostic tool in TBU. The enriched pathways generate interesting hypotheses and drive further research.
AB - Objective: To elucidate disease-specific host protein profile in vitreous fluid of patients with intraocular inflammation due to tubercular uveitis (TBU). Methods: Vitreous samples from 13 patients with TBU (group A), 7 with non-TBU (group B) and 9 with no uveitis (group C) were analysed by shotgun proteomics using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) were subjected to pathway analysis using WEB-based Gene SeT Analysis Toolkit software. Results: Compared to control groups (B + C combined), group A (TBU) displayed 32 (11 upregulated, 21 downregulated) DEPs, which revealed an upregulation of coagulation cascades, complement and classic pathways, and downregulation of metabolism of carbohydrates, gluconeogenesis, glucose metabolism and glycolysis/gluconeogenesis pathways. When compared to group B (non-TBU) alone, TBU displayed 58 DEPs (21 upregulated, 37 downregulated), with an upregulation of apoptosis, KRAS signaling, diabetes pathways, classic pathways, and downregulation of MTORC1 signaling, glycolysis/gluconeogenesis, and glucose metabolism. Conclusion: This differential protein profile provides novel insights into the molecular mechanisms of TBU and a baseline to explore vitreous biomarkers to differentiate TBU from non-TBU, warranting future studies to identify and validate them as a diagnostic tool in TBU. The enriched pathways generate interesting hypotheses and drive further research.
KW - Extrapulmonary tuberculosis
KW - Shotgun proteomics
KW - Tubercular uveitis
KW - Tuberculosis
KW - Uveitis
KW - Vitreous
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U2 - 10.1016/j.tube.2020.102036
DO - 10.1016/j.tube.2020.102036
M3 - Article
C2 - 33359883
AN - SCOPUS:85097870473
SN - 1472-9792
VL - 126
JO - Tuberculosis
JF - Tuberculosis
M1 - 102036
ER -