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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| Format: | Article |
| Language: | English |
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Dove Medical Press
2020-10-01
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| Series: | Clinical Ophthalmology |
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| Online Access: | https://www.dovepress.com/differential-mirna-expression-signature-for-glaucoma-in-pseudoexfoliat-peer-reviewed-article-OPTH |
| _version_ | 1818845249715306496 |
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| 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 |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-19T05:26:40Z |
| format | Article |
| id | doaj.art-7f0b300c02414bff873877014918cc0a |
| institution | Directory Open Access Journal |
| issn | 1177-5483 |
| language | English |
| last_indexed | 2024-12-19T05:26:40Z |
| publishDate | 2020-10-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Clinical Ophthalmology |
| spelling | doaj.art-7f0b300c02414bff873877014918cc0a2022-12-21T20:34:21ZengDove Medical PressClinical Ophthalmology1177-54832020-10-01Volume 143025303857678Differential miRNA Expression: Signature for Glaucoma in PseudoexfoliationRao AChakraborty MRoy ASahay PPradhan ARaj NAparna 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 factorhttps://www.dovepress.com/differential-mirna-expression-signature-for-glaucoma-in-pseudoexfoliat-peer-reviewed-article-OPTHpseudoexfoliationpseudoexfoliation glaucopseudoexfoliationpseudoexfoliation glaucomaocular hypertensionmirnatransforming growth factor. maocular hypertensionmirnatransforming growth factor |
| spellingShingle | Rao A Chakraborty M Roy A Sahay P Pradhan A Raj N Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation Clinical Ophthalmology pseudoexfoliation pseudoexfoliation glaucopseudoexfoliation pseudoexfoliation glaucoma ocular hypertension mirna transforming growth factor. ma ocular hypertension mirna transforming growth factor |
| title | 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_short | Differential miRNA Expression: Signature for Glaucoma in Pseudoexfoliation |
| title_sort | differential mirna expression signature for glaucoma in pseudoexfoliation |
| topic | pseudoexfoliation pseudoexfoliation glaucopseudoexfoliation pseudoexfoliation glaucoma ocular hypertension mirna transforming growth factor. ma ocular hypertension mirna transforming growth factor |
| url | https://www.dovepress.com/differential-mirna-expression-signature-for-glaucoma-in-pseudoexfoliat-peer-reviewed-article-OPTH |
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