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

Abstract

Purpose 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. Methods 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. Results 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. Conclusions 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.