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Published on: July 22, 2014
Serum miRNA modulations indicate changes in retinal morphology
Riemke Aggio-Bruce1,2, Ulrike Schumann1,3, Adrian V Cioanca1
1The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia.
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.
Insights
Serum microRNAs (miRNAs) show promise as early diagnostic biomarkers for age-related macular degeneration (AMD). This study identified a preliminary serum miRNA signature for AMD progression by combining mouse models and human patient data.
Area of Science:
- Ophthalmology
- Biomarker Discovery
- Molecular Biology
Background:
- Age-related macular degeneration (AMD) is a leading cause of vision loss, diagnosed via retinal morphology.
- MicroRNAs (miRNAs) are explored as biomarkers for neurological diseases, including AMD, but studies lack overlap due to biological complexity and varied designs.
- A novel approach using preclinical models and clinical samples is needed to establish a reliable serum signature for AMD progression.
Purpose of the Study:
- To determine a serum signature indicative of age-related macular degeneration (AMD) progression.
- To validate the use of serum microRNAs (miRNAs) as early diagnostic biomarkers for retinal degeneration.
- To investigate the overlap of miRNA expression changes between a preclinical mouse model and human AMD patients.
Main Methods:
- Serum miRNAs were extracted from mice subjected to photo-oxidative damage and from human patients with AMD.
- ~800 miRNAs were quantified using OpenArray™, with differential abundance analyzed using HTqPCR and DAVID.
- MiRNA expression changes were correlated with retinal histological indicators and compared between the mouse model and human samples.
Main Results:
- Differential miRNA abundance was detected in both the mouse model and human AMD samples, correlating with inflammatory pathways and retinal histological changes.
- Findings in the mouse serum samples were successfully aligned with those observed in clinical patient samples.
- A preliminary serum miRNA signature associated with AMD progression was identified.
Conclusions:
- Serum miRNAs serve as a valid diagnostic tool, reflecting retinal health changes for early detection of degeneration.
- The combined approach of preclinical models and human samples identified a preliminary serum miRNA signature for AMD.
- This study provides a foundation for developing a diagnostic serum miRNA panel for early AMD detection.
