PMID- 33914756 OWN - NLM STAT- MEDLINE DCOM- 20211012 LR - 20211012 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 16 IP - 4 DP - 2021 TI - TGFbeta1, MMPs and cytokines profiles in ocular surface: Possible tear biomarkers for pseudoexfoliation. PG - e0249759 LID - 10.1371/journal.pone.0249759 [doi] LID - e0249759 AB - PURPOSE: Pseudoexfoliation (PXF) is a unique form of glaucoma characterized by accumulation of exfoliative material in the eyes. Changes in tear profile in disease stages may give us insights into molecular mechanisms involved in causing glaucoma in the eye. METHODS: All patients were categorized into three main categories; pseudoexfoliation (PXF), pseudoexfoliation glaucoma (PXG) and cataract, which served as control. Cytokines, transforming growth factor beta1 (TGFbeta1), matrix metalloproteases (MMPs) and fibronectin (FN1) were assessed with multiplex bead assay, enzyme-linked immunosorbent assay (ELISA), gelatin zymography, and immunohistochemistry (IHC) respectively in different ocular tissues such as tears, tenon's capsule, aqueous humor (AH) and serum samples of patients with PXF stages. RESULTS: We found that TGFbeta1, MMP-9 and FN1 protein expression were upregulated in tears, tenon's capsule and AH samples in PXG compared to PXF, though the MMP-9 protein activity was downregulated in PXG compared with control or PXF. We have also found that in PXG tears sample the fold change of TGF-alpha (Transforming Growth Factor-alpha), MDC (Macrophage Derived Chemokine), IL-8 (Interleukin-8), VEGF (Vascular Endothelial Growth Factor) were significantly downregulated and the levels of GM-CSF (Granulocyte Macrophage Colony Stimulating Factor), IP-10 (Interferon- gamma produced protein-10) were significant upregulated. While in AH; IL-6 (Interleukin-6), IL-8, VEGF, IFN-a2 (Interferon- alpha2), GRO (Growth regulated alpha protein) levels were found lower and IL1a (Interleukin-1alpha) level was higher in PXG compared to PXF. And in serum; IFN-a2, Eotaxin, GM-CSF, Fractalkine, IL-10 (Interleukin-10), IL1Ra (Interleukin-1 receptor antagonist), IL-7 (Interleukin-7), IL-8, MIP1beta (Macrophage Inflammatory Protein-1beta), MCP-1 (Monocyte Chemoattractant Protein-1) levels were significantly upregulated and PDGF-AA (Platelet Derived Growth Factor-AA) level was downregulated in the patients with PXG compared to PXF. CONCLUSIONS: Altered expression of these molecules in tears may therefore be used as a signal for onset of glaucoma or for identifying eyes at risk of developing glaucoma in PXF. FAU - Sahay, Prity AU - Sahay P AD - Hyderabad Eye Research Foundation (HERF), L.V. Prasad Eye Institute, Patia, Bhubaneswar, Odisha, India. AD - KIIT School of Biotechnology, Patia, Bhubaneswar, Odisha, India. FAU - Reddy, Shweta AU - Reddy S AD - Hyderabad Eye Research Foundation (HERF), L.V. Prasad Eye Institute, Patia, Bhubaneswar, Odisha, India. FAU - Prusty, Birendra Kumar AU - Prusty BK AD - Institute of Life Science, Bhubaneswar, Odisha, India. FAU - Modak, Rahul AU - Modak R AD - KIIT School of Biotechnology, Patia, Bhubaneswar, Odisha, India. FAU - Rao, Aparna AU - Rao A AUID- ORCID: 0000-0001-8120-8740 AD - Hyderabad Eye Research Foundation (HERF), L.V. Prasad Eye Institute, Patia, Bhubaneswar, Odisha, India. AD - KIIT School of Biotechnology, Patia, Bhubaneswar, Odisha, India. LA - eng GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210429 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (TGFB1 protein, human) RN - 0 (Transforming Growth Factor beta1) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Biomarkers/*metabolism MH - Cytokines/*metabolism MH - Exfoliation Syndrome/diagnosis/*metabolism/pathology MH - Eye/*metabolism/pathology MH - Female MH - Humans MH - Male MH - Matrix Metalloproteinases/*metabolism MH - Middle Aged MH - Tears/*metabolism MH - Transforming Growth Factor beta1/*metabolism PMC - PMC8084233 COIS- The authors have declared that no competing interests exist. EDAT- 2021/04/30 06:00 MHDA- 2021/10/13 06:00 PMCR- 2021/04/29 CRDT- 2021/04/29 17:31 PHST- 2021/01/12 00:00 [received] PHST- 2021/03/24 00:00 [accepted] PHST- 2021/04/29 17:31 [entrez] PHST- 2021/04/30 06:00 [pubmed] PHST- 2021/10/13 06:00 [medline] PHST- 2021/04/29 00:00 [pmc-release] AID - PONE-D-21-01128 [pii] AID - 10.1371/journal.pone.0249759 [doi] PST - epublish SO - PLoS One. 2021 Apr 29;16(4):e0249759. doi: 10.1371/journal.pone.0249759. eCollection 2021.