Expressions of Serum lncRNAs in Diabetic Retinopathy – A Potential Diagnostic Tool

Saumik Biswas; Ali Coyle; Shali Chen; Miso Gostimir; John Gonder; Subrata Chakrabarti

doi:10.3389/fendo.2022.851967

Frontiers in Endocrinology (Apr 2022)

Expressions of Serum lncRNAs in Diabetic Retinopathy – A Potential Diagnostic Tool

Saumik Biswas,
Ali Coyle,
Shali Chen,
Miso Gostimir,
John Gonder,
Subrata Chakrabarti

Affiliations

Saumik Biswas: Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada
Ali Coyle: School of Biomedical Engineering, Western University, London, ON, Canada
Shali Chen: Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada
Miso Gostimir: Department of Ophthalmology, Western University, London, ON, Canada
John Gonder: Department of Ophthalmology, Western University, London, ON, Canada
Subrata Chakrabarti: Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada

DOI: https://doi.org/10.3389/fendo.2022.851967
Journal volume & issue: Vol. 13

Abstract

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With increasing incidence of diabetes worldwide, there is an ever-expanding number of patients with chronic diabetic complications such as diabetic retinopathy (DR), one of the leading causes of blindness in the working age population. Early screening for the onset and severity of DR is essential for timely intervention. With recent advancements in genomic technologies, epigenetic alterations in DR are beginning to unravel. Long non-coding RNAs (lncRNAs), which are key epigenetic mediators, have demonstrated implications in several (DR) related processes. Based on the previous research, we have developed a serum-based, multi-panel PCR test using 9 lncRNAs (ANRIL, MALAT1, WISPER, ZFAS1, H19, HOTAIR, HULC, MEG3, and MIAT) to identify and validate whether this panel could be used as a diagnostic and prognostic tool for DR. We initially used a cell culture model (human retinal endothelial cells) and confirmed that 25 mM glucose induces upregulations of ANRIL, HOTAIR, HULC, MALAT1, and ZFAS1, and downregulation of H19 compared to 5 mM glucose controls. Then as an initial proof-of-concept, we tested vitreous humor and serum samples from a small cohort of non-diabetic (N=10) and diabetic patients with proliferative retinopathy (PDR, N=11) and measured the levels of the 9 lncRNAs. Differential expressions of lncRNAs were found in the vitreous and serum of patients and showed significant correlations. We expanded our approach and assessed the same lncRNAs using samples from a larger cohort of diabetic (n= 59; M/F:44/15) and non-diabetic patients (n= 11; M/F:4/7). Significant increased lncRNA expressions of ANRIL, H19, HOTAIR, HULC, MIAT, WISPER and ZFAS1 were observed in the serum of diabetic patients (with varying stages of DR) compared to non-diabetics. No significant correlations were demonstrated between lncRNA expressions and creatinine or glycated hemoglobin (HbA1C) levels. Using ROC and further analyses, we identified distinct lncRNA phenotype combinations, which may be used to identify patients with DR. Data from this study indicate that a panel of serum lncRNAs may be used for a potential screening test for DR. Further large-scale studies are needed to validate this notion.

Published in Frontiers in Endocrinology

ISSN: 1664-2392 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the endocrine glands. Clinical endocrinology
Website: https://www.frontiersin.org/journals/endocrinology

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