title: Inner Segment Remodeling and Mitochondrial Translocation in Cone Photoreceptors in Age-Related Macular Degeneration With Outer Retinal Tubulation.
abstract: OBJECTIVE
  To quantify impressions of mitochondrial translocation in degenerating cones and to determine the nature of accumulated material in the subretinal space with apparent inner segment (IS)-like features by examining cone IS ultrastructure.
  
  
  METHODS
  Human donor eyes with advanced age-related macular degeneration (AMD) were screened for outer retinal tubulation (ORT) in macula-wide, high-resolution digital sections. Degenerating cones inside ORT (ORT cones) and outside ORT (non-ORT cones) from AMD eyes and unaffected cones in age-matched control eyes were imaged using transmission electron microscopy. The distances of mitochondria to the external limiting membrane (ELM), cone IS length, and cone IS width at the ELM were measured.
  
  
  RESULTS
  Outer retinal tubulation and non-ORT cones lose outer segments (OS), followed by shortening of IS and mitochondria. In non-ORT cones, IS broaden. Outer retinal tubulation and non-ORT cone IS myoids become undetectable due to mitochondria redistribution toward the nucleus. Some ORT cones were found lacking IS and containing mitochondria in the outer fiber (between soma and ELM). Unlike long, thin IS mitochondria in control cones, ORT and non-ORT IS mitochondria are ovoid or reniform. Shed IS, some containing mitochondria, were found in the subretinal space.
  
  
  CONCLUSIONS
  In AMD, macula cones exhibit loss of detectable myoid due to IS shortening in addition to OS loss, as described. Mitochondria shrink and translocate toward the nucleus. As reflectivity sources, translocating mitochondria may be detectable using in vivo imaging to monitor photoreceptor degeneration in retinal disorders. These results improve the knowledge basis for interpreting high-resolution clinical retinal imaging.
authors.affiliation: Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama, United States 2Vision Science Graduate Program, University of Alabama at Birmingham, Birmingham, Alabama, United States.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Litts
authors.affiliation: Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama, United States.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Messinger
authors.affiliation: Vitreous Retina Macula Consultants of New York, New York City, New York, United States.
authors.forename: K Bailey
authors.initials: KB
authors.lastname: Freund
authors.affiliation: Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama, United States.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, Alabama, United States.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Curcio
mesh_terms: D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000473:pathology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000648:ultrastructure*; D017949:Retinal Cone Photoreceptor Cells / Q000648:ultrastructure*; D055211:Retinal Photoreceptor Cell Inner Segment / Q000648:ultrastructure*; D041623:Tomography, Optical Coherence