Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation

Aparna Rao,* Munmun Chakraborty,* AkashSingha Roy,* Prity Sahay, Amiya Pradhan, Niranjan Raj Glaucoma Service, LV Prasad Eye Institute, Bhubaneswar, Odisha 751024, India*These authors contributed equally to this workCorrespondence: Aparna RaoLV Prasad Eye Institute, Patia, Bhubaneswar, IndiaTel +91...

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Autores principales:	Rao A, Chakraborty M, Roy A, Sahay P, Pradhan A, Raj N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	pseudoexfoliation pseudoexfoliation glaucopseudoexfoliation pseudoexfoliation glaucoma ocular hypertension mirna transforming growth factor. ma transforming growth factor Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/7f0b300c02414bff873877014918cc0a
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spelling	oai:doaj.org-article:7f0b300c02414bff873877014918cc0a2021-12-02T12:22:21ZDifferential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation1177-5483https://doaj.org/article/7f0b300c02414bff873877014918cc0a2020-10-01T00:00:00Zhttps://www.dovepress.com/differential-mirna-expression-signature-for-glaucoma-in-pseudoexfoliat-peer-reviewed-article-OPTHhttps://doaj.org/toc/1177-5483Aparna Rao,* Munmun Chakraborty,* AkashSingha Roy,* Prity Sahay, Amiya Pradhan, Niranjan Raj Glaucoma Service, LV Prasad Eye Institute, Bhubaneswar, Odisha 751024, India*These authors contributed equally to this workCorrespondence: Aparna RaoLV Prasad Eye Institute, Patia, Bhubaneswar, IndiaTel +91 674 398 7999/7201Fax +91 674 398 7130Email aparna@lvpei.orgPurpose: To investigate the microRNA (miRNA) profile in patients with different stages of pseudoexfoliation (PXF).Methods: Peripheral blood of patients with PXF (naïve to medical therapy and with no systemic disease/drugs) with ocular hypertension (OHT) and pseudoexfoliation glaucoma (PXG) was evaluated in triplicate for miRNA profiling using polymerase chain reaction (PCR) arrays. Those identified in the discovery stage were validated with evaluation of serum transforming growth factor-β 1 (TGF-β 1) levels by ELISA. The downstream targets of TGF-β 1 and unfolded protein response (UPR) were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Predicted targets of the identified miRNA and KEGG pathway analysis were done using miRbase and DIANA tools mirPathv3.1.Results: We found hsa-miR-122-5p, hsa-miR-124-3p and hsa-miR-424-5p to be upregulated in PXG targeting 3 specific pathways namely TGF-β 1, fibrosis/ECM and proteoglycan metabolism with common effectors like SMAD/3/2. The unfolded protein response (UPR) genes were significantly downregulated in all stages of PXF suggesting this as the key mechanism for protein aggregates in PXF syndrome. Serum TGF-β 1 was significantly upregulated as disease progressed to later stages in PXG. This elevation in advanced stages was associated with significantly differential expression of downstream pathways and fibrotic genes in OHT compared to PXG predominantly through the SMAD3, a canonical pathway marker.Conclusion: Circulatory miRNA differentially regulating TGF-β 1 and downstream targets including UPR genes may be the key mechanisms for glaucoma onset in PXF.Keywords: pseudoexfoliation, pseudoexfoliation glaucoma, ocular hypertension, miRNA, transforming growth factorRao AChakraborty MRoy ASahay PPradhan ARaj NDove Medical Pressarticlepseudoexfoliationpseudoexfoliation glaucopseudoexfoliationpseudoexfoliation glaucomaocular hypertensionmirnatransforming growth factor. maocular hypertensionmirnatransforming growth factorOphthalmologyRE1-994ENClinical Ophthalmology, Vol Volume 14, Pp 3025-3038 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	pseudoexfoliation pseudoexfoliation glaucopseudoexfoliation pseudoexfoliation glaucoma ocular hypertension mirna transforming growth factor. ma ocular hypertension mirna transforming growth factor Ophthalmology RE1-994
spellingShingle	pseudoexfoliation pseudoexfoliation glaucopseudoexfoliation pseudoexfoliation glaucoma ocular hypertension mirna transforming growth factor. ma ocular hypertension mirna transforming growth factor Ophthalmology RE1-994 Rao A Chakraborty M Roy A Sahay P Pradhan A Raj N Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation
description	Aparna Rao,* Munmun Chakraborty,* AkashSingha Roy,* Prity Sahay, Amiya Pradhan, Niranjan Raj Glaucoma Service, LV Prasad Eye Institute, Bhubaneswar, Odisha 751024, India*These authors contributed equally to this workCorrespondence: Aparna RaoLV Prasad Eye Institute, Patia, Bhubaneswar, IndiaTel +91 674 398 7999/7201Fax +91 674 398 7130Email aparna@lvpei.orgPurpose: To investigate the microRNA (miRNA) profile in patients with different stages of pseudoexfoliation (PXF).Methods: Peripheral blood of patients with PXF (naïve to medical therapy and with no systemic disease/drugs) with ocular hypertension (OHT) and pseudoexfoliation glaucoma (PXG) was evaluated in triplicate for miRNA profiling using polymerase chain reaction (PCR) arrays. Those identified in the discovery stage were validated with evaluation of serum transforming growth factor-β 1 (TGF-β 1) levels by ELISA. The downstream targets of TGF-β 1 and unfolded protein response (UPR) were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Predicted targets of the identified miRNA and KEGG pathway analysis were done using miRbase and DIANA tools mirPathv3.1.Results: We found hsa-miR-122-5p, hsa-miR-124-3p and hsa-miR-424-5p to be upregulated in PXG targeting 3 specific pathways namely TGF-β 1, fibrosis/ECM and proteoglycan metabolism with common effectors like SMAD/3/2. The unfolded protein response (UPR) genes were significantly downregulated in all stages of PXF suggesting this as the key mechanism for protein aggregates in PXF syndrome. Serum TGF-β 1 was significantly upregulated as disease progressed to later stages in PXG. This elevation in advanced stages was associated with significantly differential expression of downstream pathways and fibrotic genes in OHT compared to PXG predominantly through the SMAD3, a canonical pathway marker.Conclusion: Circulatory miRNA differentially regulating TGF-β 1 and downstream targets including UPR genes may be the key mechanisms for glaucoma onset in PXF.Keywords: pseudoexfoliation, pseudoexfoliation glaucoma, ocular hypertension, miRNA, transforming growth factor
format	article
author	Rao A Chakraborty M Roy A Sahay P Pradhan A Raj N
author_facet	Rao A Chakraborty M Roy A Sahay P Pradhan A Raj N
author_sort	Rao A
title	Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation
title_short	Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation
title_full	Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation
title_fullStr	Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation
title_full_unstemmed	Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation
title_sort	differential mirna expression: signature for glaucoma in pseudoexfoliation
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/7f0b300c02414bff873877014918cc0a
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_version_	1718394462139318272

Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation

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