April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Histologic Correlates of Reflectivity of Outer Retinal Tubulations (ORT) in Age-Related Macular Degeneration (AMD)
Author Affiliations & Notes
  • Katie M Litts
    Vision Sciences, Univ of Alabama at Birmingham, Birmingham, AL
  • Jeffrey D Messinger
    Ophthalmology, Univ of Alabama at Birmingham, Birmingham, AL
  • Yuhua Zhang
    Ophthalmology, Univ of Alabama at Birmingham, Birmingham, AL
  • Christine A Curcio
    Ophthalmology, Univ of Alabama at Birmingham, Birmingham, AL
  • Footnotes
    Commercial Relationships Katie Litts, None; Jeffrey Messinger, None; Yuhua Zhang, None; Christine Curcio, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4016. doi:
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    • Get Citation

      Katie M Litts, Jeffrey D Messinger, Yuhua Zhang, Christine A Curcio; Histologic Correlates of Reflectivity of Outer Retinal Tubulations (ORT) in Age-Related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2014;55(13):4016.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

ORT are tubular scars formed by Müller cells and cone photoreceptors {1, 2} with lumens delimited by the external limiting membrane (ELM, Figure B). We evaluated inner segment (IS) ultrastructure in ORT cones and degenerating cones outside ORT (nonORT), focusing on IS ellipsoid mitochondria (Mito), a hypothesized correlate for the ORT hyper-reflective border in optical coherence tomography (OCT) {3}.

 
Methods
 

Human eyes (40 exudative AMD; 13 geographic atrophy (GA)) from Caucasian donors were screened for ORT from macula-wide high-resolution digital sections {4}. Cones in 25 eyes (18 exudative AMD, 1 GA, 1 RPE hyperplasia) and 5 Unremarkable eyes that served as Controls were imaged using transmission electron microscopy (TEM). nonORT cones were located within the remaining mosaic of inner segments (IS), where the ELM was continuous and flat. Cones with a nucleus and connected to IS through the ELM were selected for imaging. Mito distance (location of Mito centroid relative to ELM), IS length, and width at the ELM were measured using ImageJ.

 
Results
 

ORT and nonORT cones appear to degenerate similarly, with loss of outer segments, followed by shortening of IS and Mito, and in nonORT cones, IS broadening (Figure B, C; Table). ORT and nonORT cone IS myoids became undetectable due to inward Mito dispersion towards the nucleus (Figure C). Some ORT cones lacked IS, but contained Mito between the ELM and nucleus. Compared to long thin Control IS Mito (Figure A, green arrow), ORT and nonORT IS Mito are circular, oval, or kidney shaped (Figure C, inset).

 
Conclusions
 

This is the first systematic ultrastructural examination of degenerating macular cones in AMD. These cells exhibit IS shortening and loss of detectable myoid. Mito shrink and migrate toward the nucleus. Scattering of light by persisting Mito could explain the ellipsoid line in ORT {2}, which lack outer segments {abstract by Freund et al}. Results provide a basis for improved interpretation of high-resolution imaging including OCT and adaptive optics assisted retinal imaging. 1. Curcio PMID 8641827. 2. Zweifel PMID 20008714. 3. Spaide PMID 21844839. 4. http://projectmacula.cis.uab.edu.

 
 
Figure. Ultrastructure of cones. Control eye (A). ORT in AMD (B). nonORT in AMD(C). ELM (yellow arrows), Mito (green arrows) and inset. Bruch’s membrane (arrowheads).
 
Figure. Ultrastructure of cones. Control eye (A). ORT in AMD (B). nonORT in AMD(C). ELM (yellow arrows), Mito (green arrows) and inset. Bruch’s membrane (arrowheads).
   
Keywords: 600 mitochondria • 648 photoreceptors • 597 microscopy: electron microscopy  
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