OCT Biomarker Testing for Early Dysregulated Photoreceptor Metabolism in Dark-Reared Pde6brd10 Mice

The purpose of this study was to noninvasively test the hypothesis that dysregulated photoreceptor metabolism occurs with early retinal degeneration in dark-reared Pde6brd10 mice.

Postnatal day 23 (P23) phosphodiesterase (PDE) mutant (Pde6brd10) mice, P23 wild-type (WT) mice were continuously dark-reared, and 2-month-old dark-adapted (DA) C57BL/6J WT mice were studied following acute injection of the carbonic anhydrase inhibitor acetazolamide (ACZ) or saline control. Two optical coherence tomography (OCT) metabolic biomarkers were measured: (i) external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness, a proxy for subretinal space acidosis, and (ii) the profile shape aspect ratio of the hyper-reflective band just distal to the ELM (band 2), a proxy for mitochondrial configuration within photoreceptor inner segments. Retinal laminar thicknesses were also assessed.

P23 Pde6brd10 mice responded to ACZ with ELM-RPE contraction, but no change in band 2 profile shape aspect ratio; outer nuclear layer thickness was subnormal. In contrast, P23 WT mice showed no change in either OCT metabolic biomarker following ACZ administration. DA 2-month-old WT mice showed ELM-RPE contraction with ACZ; band 2 profile shape aspect ratio increased in male mice, with no change in female mice.

P23 Pde6brd10 mice with limited rod atrophy had biomarker values suggestive of dysregulation of RPE fluid/ion transport but with stable rod mitochondrial configuration following ACZ. DA 2-month-old male WT mice biomarkers were responsive to ACZ in a manner similar to those in light-adapted 2-month-old male WT mice; the difference in biomarker response pattern in female WT mice suggests a possible hormonal influence.