OPTICAL COHERENCE TOMOGRAPHY AND HISTOLOGY OF AGE-RELATED MACULAR DEGENERATION SUPPORT MITOCHONDRIA AS REFLECTIVITY SOURCES.

Abstract

Widespread adoption of optical coherence tomography has revolutionized the diagnosis and management of retinal disease. If the cellular and subcellular sources of reflectivity in optical coherence tomography can be identified, the value of this technology will be advanced even further toward precision medicine, mechanistic thinking, and molecular discovery. Four hyperreflective outer retinal bands are created by the exquisite arrangement of photoreceptors, Müller cells, retinal pigment epithelium, and Bruch membrane. Because of massed effects of these axially compartmentalized and transversely aligned cells, reflectivity can be localized to the subcellular level. This review focuses on the second of the four bands, called ellipsoid zone in a consensus clinical lexicon, with the central thesis that mitochondria in photoreceptor inner segments are a major independent reflectivity source in this band, because of Mie scattering and waveguiding. We review the evolution of Band 2 nomenclature in published literature and discuss the origins of imaging signals from photoreceptor mitochondria that could make these organelles visible in vivo. Our recent data pertain to outer retinal tubulation, a unique neurodegenerative and gliotic structure with a highly reflective border, prominent in late age-related macular degeneration. High-resolution histology and multimodal imaging of outer retinal tubulation together provide evidence that inner segment mitochondria undergoing fission and translocation toward the nucleus provide the reflectivity signal. Our data support adoption of the ellipsoid zone nomenclature. Identifying subcellular signal sources will newly inform clinical.