Invest Ophthalmol Vis Sci. 2026 Oct 1;67(12):28. doi: 10.1167/iovs.67.12.28.
ABSTRACT
PURPOSE: The purpose of this study was to test for abnormal optical coherence tomography (OCT) metabolic biomarker patterns in the A53T Parkinson’s disease model, which accumulates α-synuclein in photoreceptor inner segments before overt motor symptoms.
METHODS: Four-to-6-month-old transgenic A53T homozygous mice and B6C3H wild-type (WT) littermate controls were evaluated using 2 OCT metabolic biomarkers. The first was the external limiting membrane (ELM) to retinal pigment epithelium (RPE) thickness, a proxy for subretinal space acidification and retinoid deficiency. The second biomarker was the sub-ELM hyper-reflective band profile shape minor:major aspect ratio, a proxy for mitochondrial configuration within photoreceptor inner segments. We also tested for outer nuclear layer (ONL) thinning, OCT metabolic biomarker sensitivity to light-dark conditions, and nicotinamide nucleotide transhydrogenase (Nnt) expression.
RESULTS: A53T mice showed inferior and superior subnormal ELM-RPE thickness, and a supranormal sub-ELM hyper-reflective band profile shape aspect ratio in the inferior but not the superior retina. Central retinal ONL thickness was unremarkable between groups. Compared to light, dark-adaptation evoked contraction in ELM-RPE thickness and an increase in sub-ELM hyper-reflective band profile shape aspect ratio in both cohorts. In addition, B6C3H control mice expressed functional Nnt.
CONCLUSIONS: The abnormal OCT metabolic biomarker patterns raise the possibility of central outer retinal dysmetabolism in A53T mice, despite normal ONL thickness. Light-dark results show that ELM-RPE contraction can be caused by increased metabolic demand in the A53T mouse model.
PMID:42878580 | DOI:10.1167/iovs.67.12.28