The A53T Parkinson's Disease Mouse Model Shows Abnormal Outer Retinal OCT Metabolic Biomarker Patterns

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.

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.

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.

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.