June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Retinal pigment epithelium (RPE) transdifferentiation and death in age-related macular degeneration (AMD), seen in the Project MACULA grading system
Author Affiliations & Notes
  • Christine A Curcio
    Ophthalmology, Univ of Alabama at Birmingham, Birmingham, AL
  • Emma C. Zanzottera
    Ophthalmology, Univ of Alabama at Birmingham, Birmingham, AL
    Ophthalmology, University of Milan, Milan, Italy
  • Jeffrey D Messinger
    Ophthalmology, Univ of Alabama at Birmingham, Birmingham, AL
  • Thomas Ach
    Ophthalmology, Univ of Alabama at Birmingham, Birmingham, AL
  • Theodore Smith
    Ophthalmology, New York University, New York, NY
  • K Bailey Freund
    Vitreous Retina Macula Consultants, New York, NY
  • Footnotes
    Commercial Relationships Christine Curcio, None; Emma Zanzottera, None; Jeffrey Messinger, None; Thomas Ach, None; Theodore Smith, None; K Bailey Freund, Bayer Health Care (C), Genentech (C), Heidelberg Engineering (C), Regeneron (C), Thrombogenics (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 893. doi:
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    • Get Citation

      Christine A Curcio, Emma C. Zanzottera, Jeffrey D Messinger, Thomas Ach, Theodore Smith, K Bailey Freund; Retinal pigment epithelium (RPE) transdifferentiation and death in age-related macular degeneration (AMD), seen in the Project MACULA grading system. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):893.

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

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Abstract
 
Purpose
 

To seek pathways of RPE transdifferentiation and death in AMD via a system of discretized morphology; to correlate RPE morphologies with spectral domain optical coherence tomography (SDOCT); to provide nomenclature, visualization targets, and metrics for clinical imaging and model systems.

 
Methods
 

Eyes from white donors with geographic atrophy (GA) or choroidal neovascularization (CNV) and one eye of a 98-year-old donor with GA and previous clinical SDOCT were processed for macula-wide high-resolution sections (http://projectmacula). Sections through the fovea and superior perifovea were photodocumented. Thicknesses of RPE and basal laminar deposit (BLamD) were measured at standard locations (Curcio PMID 23266879). RPE cells contained spindle-shaped melanosomes, adjacent to a basal lamina or BLamD. Cells containing melanosomes, or derived from such cells, not adjacent to BLamD, were considered RPE-derived and studied separately.

 
Results
 

In 449 locations in 13 eyes with GA and 1363 locations in 39 eyes with CNV, 9 RPE morphologies were found: Non-uniform; Very non-uniform; Sloughing (into subretinal space with epithelium remaining); Intraretinal (internal to external limiting membrane, with epithelium remaining); Shedding (into BLamD); Bilaminar; Vacuolated; Dissociated; Entombed (within scars). In GA eyes, 22% of atrophic locations had Dissociated cells, likely derived from epithelioid cells of Sloughing and Shedding forms. In CNV eyes, 37 % of locations with scar had Entombed RPE. Shedding and Dissociated cells released non-nucleated granule aggregations into BLamD. The RPE layer did not thin, and BLamD remained thick, with advanced pathology. Four forms correlated to SDOCT hyper-reflectivities in the previously examined GA patient.

 
Conclusions
 

A system of RPE cell morphologies applicable to both GA and CNV indicate that the RPE has multiple pathways of transdifferentiation and death (Figure). The atrophic area has numerous cells capable of transcribing genes and generating imaging signals. Shed granule aggregates originate intracellularly, have distinctive autofluorescence (Ach ARVO2014; BenAmi, abstract submitted), are visible in SDOCT, and may represent apoptotic bodies. The significance of RPE phenotypes can be determined in longitudinal, high-resolution imaging in clinic populations.  

 
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