Serum miRNA modulations indicate changes in retinal morphology

Riemke Aggio-Bruce; Ulrike Schumann; Adrian V Cioanca; Fred K Chen; Samuel McLenachan; Rachael C Heath Jeffery; Shannon Das; Riccardo Natoli

doi:10.3389/fnmol.2023.1130249

Serum miRNA modulations indicate changes in retinal morphology

Front Mol Neurosci. 2023 Mar 3:16:1130249. doi: 10.3389/fnmol.2023.1130249. eCollection 2023.

Authors

Riemke Aggio-Bruce^{1

2}, Ulrike Schumann^{1

3}, Adrian V Cioanca¹, Fred K Chen^{4

5

6

7}, Samuel McLenachan^{4

5}, Rachael C Heath Jeffery^{4

5

7}, Shannon Das¹, Riccardo Natoli^{1

2}

Affiliations

¹ The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia.
² The School of Medicine and Psychology, Acton, ACT, Australia.
³ The Save Sight Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
⁴ Centre of Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, Australia.
⁵ Lions Eye Institute, Perth, WA, Australia.
⁶ Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, Australia.
⁷ Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia.

Abstract

Background: Age-related macular degeneration (AMD) is the leading cause of vision loss in the developed world and the detection of its onset and progression are based on retinal morphological assessments. MicroRNA (miRNA) have been explored extensively as biomarkers for a range of neurological diseases including AMD, however differences in experimental design and the complexity of human biology have resulted in little overlap between studies. Using preclinical animal models and clinical samples, this study employs a novel approach to determine a serum signature of AMD progression.

Methods: Serum miRNAs were extracted from mice exposed to photo-oxidative damage (PD; 0, 1, 3 and 5 days), and clinical samples from patients diagnosed with reticular pseudodrusen or atrophic AMD. The expression of ~800 miRNAs was measured using OpenArray™, and differential abundance from controls was determined using the HTqPCR R package followed by pathway analysis with DAVID. MiRNA expression changes were compared against quantifiable retinal histological indicators. Finally, the overlap of miRNA changes observed in the mouse model and human patient samples was investigated.

Results: Differential miRNA abundance was identified at all PD time-points and in clinical samples. Importantly, these were associated with inflammatory pathways and histological changes in the retina. Further, we were able to align findings in the mouse serum to those of clinical patients.

Conclusion: In conclusion, serum miRNAs are a valid tool as diagnostics for the early detection of retinal degeneration, as they reflect key changes in retinal health. The combination of pre-clinical animal models and human patient samples led to the identification of a preliminary serum miRNA signature for AMD. This study is an important platform for the future development of a diagnostic serum miRNA panel for the early detection of retinal degeneration.

Keywords: age-related macular degeneration; diagnostics; microRNA; neurodegeneration; serum miRNAs.