Transcriptomic Analysis of Plasma-derived Small Extracellular Vesicles Reveals the Pathological Characteristics of Normal Tension Glaucoma

Overview

Journal Extracell Vesicles Circ Nucl Acids

Date 2024 Dec 19

PMID 39697633

Authors

Sheng-Lan Xu

Jun-Hua Li

Wen-Meng Zhang

Meng-Jun Fu

Hui-Min Xing

Hua Ma

Xian-Hui Gong

Rong-Han Wu

Yuan-Bo Liang

Ren-Zhe Cui

Zai-Long Chi

Affiliations

Soon will be listed here.

Abstract

Aim: Normal tension glaucoma (NTG) is a common optic neuropathy that can be challenging to diagnose due to the intraocular pressure remaining within the normal range. Early diagnosis and intervention are crucial for the effective lifelong management of patients.

Methods: This study recruited a total of 225 participants. Small extracellular vesicles (sEVs) RNA from circulating plasma was analyzed via transcriptomic sequencing, and its expression levels were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Logistic regression, linear regression, and receiver operating characteristic (ROC) curve analyses were performed to examine the association of biomarkers with clinicopathological characteristics.

Results: Analysis of sEVs mRNAs in NTG patients revealed mitochondrial dysfunction and enrichment of central nervous system degenerative pathways, reflecting the pathological features of NTG. Compared with those in the controls, the expression levels of sEVs let-7b-5p in the plasma of NTG patients were significantly lower, with an area under the curve (AUC) of 0.870 (95%CI: 0.797-0.943) ( < 0.0001), and the AUC combined with age was 0.923 (95%CI: 0.851-0.996) ( < 0.0001). In addition, we found that let-7b-5p levels were significantly correlated with the severity and visual field defects of NTG patients and had good specificity compared with other ophthalmic diseases.

Conclusion: The sEVs RNA signatures in circulating plasma from NTG revealed mitochondrial dysfunction and that sEVs let-7b-5p can be a useful noninvasive biomarker for NTG.

References

Lu J, Sharma L, Bai Y . Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis. Cell Res. 2009; 19(7):802-15. PMC: 4710094. DOI: 10.1038/cr.2009.69. View

Wareham L, Calkins D . The Neurovascular Unit in Glaucomatous Neurodegeneration. Front Cell Dev Biol. 2020; 8:452. PMC: 7325980. DOI: 10.3389/fcell.2020.00452. View

Jonas J, Aung T, Bourne R, Bron A, Ritch R, Panda-Jonas S . Glaucoma. Lancet. 2017; 390(10108):2183-2193. DOI: 10.1016/S0140-6736(17)31469-1. View

Yang P, Song F, Yang X, Yan X, Huang X, Qiu Z . Exosomal MicroRNA signature acts as an efficient biomarker for non-invasive diagnosis of gallbladder carcinoma. iScience. 2022; 25(9):104816. PMC: 9420508. DOI: 10.1016/j.isci.2022.104816. View

Hirooka K, Yamamoto T, Kiuchi Y . Dysfunction of axonal transport in normal-tension glaucoma: a biomarker of disease progression and a potential therapeutic target. Neural Regen Res. 2020; 16(3):506-507. PMC: 7996034. DOI: 10.4103/1673-5374.293145. View

Kalluri R, LeBleu V . The biology function and biomedical applications of exosomes. Science. 2020; 367(6478). PMC: 7717626. DOI: 10.1126/science.aau6977. View

McKiernan J, Donovan M, Margolis E, Partin A, Carter B, Brown G . A Prospective Adaptive Utility Trial to Validate Performance of a Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer in Patients with Prostate-specific Antigen 2-10ng/ml at Initial Biopsy. Eur Urol. 2018; 74(6):731-738. DOI: 10.1016/j.eururo.2018.08.019. View

Razeghinejad M, Lee D . Managing normal tension glaucoma by lowering the intraocular pressure. Surv Ophthalmol. 2018; 64(1):111-116. DOI: 10.1016/j.survophthal.2018.07.003. View

Han S, Zhang M, Jeong Y, Margolis D, Cai Q . The role of mitophagy in the regulation of mitochondrial energetic status in neurons. Autophagy. 2021; 17(12):4182-4201. PMC: 8726713. DOI: 10.1080/15548627.2021.1907167. View

10.

Hubens W, Krauskopf J, Beckers H, Kleinjans J, Webers C, Gorgels T . Small RNA Sequencing of Aqueous Humor and Plasma in Patients With Primary Open-Angle Glaucoma. Invest Ophthalmol Vis Sci. 2021; 62(7):24. PMC: 8237107. DOI: 10.1167/iovs.62.7.24. View

11.

Pan Y, Suga A, Kimura I, Kimura C, Minegishi Y, Nakayama M . METTL23 mutation alters histone H3R17 methylation in normal-tension glaucoma. J Clin Invest. 2022; 132(21). PMC: 9621137. DOI: 10.1172/JCI153589. View

12.

Rowe S, Maclean C, Shekelle P . Preventing visual loss from chronic eye disease in primary care: scientific review. JAMA. 2004; 291(12):1487-95. DOI: 10.1001/jama.291.12.1487. View

13.

Wostyn P, Van Dam D, De Deyn P . Alzheimer's disease and glaucoma: Look-alike neurodegenerative diseases. Alzheimers Dement. 2019; 15(4):600-601. DOI: 10.1016/j.jalz.2018.12.012. View

14.

Sen S, Saxena R, Tripathi M, Vibha D, Dhiman R . Neurodegeneration in Alzheimer's disease and glaucoma: overlaps and missing links. Eye (Lond). 2020; 34(9):1546-1553. PMC: 7608361. DOI: 10.1038/s41433-020-0836-x. View

15.

McKiernan J, Donovan M, ONeill V, Bentink S, Noerholm M, Belzer S . A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy. JAMA Oncol. 2016; 2(7):882-9. DOI: 10.1001/jamaoncol.2016.0097. View

16.

Leung D, Tham C . Normal-tension glaucoma: Current concepts and approaches-A review. Clin Exp Ophthalmol. 2022; 50(2):247-259. DOI: 10.1111/ceo.14043. View

17.

Verma M, Lizama B, Chu C . Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration. Transl Neurodegener. 2022; 11(1):3. PMC: 8788129. DOI: 10.1186/s40035-021-00278-7. View

18.

Budnik V, Ruiz-Canada C, Wendler F . Extracellular vesicles round off communication in the nervous system. Nat Rev Neurosci. 2016; 17(3):160-72. PMC: 4989863. DOI: 10.1038/nrn.2015.29. View

19.

Lee C, Larson E, Gibbons L, Lee A, McCurry S, Bowen J . Associations between recent and established ophthalmic conditions and risk of Alzheimer's disease. Alzheimers Dement. 2018; 15(1):34-41. PMC: 6333518. DOI: 10.1016/j.jalz.2018.06.2856. View

20.

Zhao J, Solano M, Oldenburg C, Liu T, Wang Y, Wang N . Prevalence of Normal-Tension Glaucoma in the Chinese Population: A Systematic Review and Meta-Analysis. Am J Ophthalmol. 2018; 199:101-110. DOI: 10.1016/j.ajo.2018.10.017. View