Enhanced Detection of Sub-Retinal Pigment Epithelial Cell Layer Deposits in Human and Murine Tissue: Imaging Zinc as a Biomarker for Age-Related Macular Degeneration (An American Ophthalmological Society Thesis).
Trans Am Ophthalmol Soc
; 115: T3, 2017 Aug.
Article
en En
| MEDLINE
| ID: mdl-29021717
ABSTRACT
PURPOSE:
Understanding the apparent paradoxical role of zinc in the pathogenesis and prevention of age-related macular degeneration (AMD) has been limited by the lack of animal models for its detection in sub-retinal epithelial deposits (drusen), a definitive early hallmark of AMD. In-vitro studies using Zinpyr-1 showed drusen contained high levels of zinc, but the probe was not suitable for in-vivo studies. This study compares Zinpyr-1 to ZPP1, a new fluorescein-based probe for zinc, to assess the potential of ZPP1 for in-vivo detection of zinc in drusen.METHODS:
Flat mounts of human sub-RPE tissue using the probes were analyzed by fluorescence and confocal microscopy. Flat mounts of sub-RPE tissue from mice deficient in superoxide dismutase isoform-1 (CuZn-SOD-KO) or isoform-2 (Mn-SOD-RPE-KO) were analyzed with sub-RPE deposits confirmed by histology.RESULTS:
Drusen are detected in greater numbers and intensity with ZPP1 compared to Zinpyr-1. Using ZPP1, drusen was detected in a sample from a 46-year old human donor without ocular history, suggesting that ZPP1 might be sensitive enough to detect drusen at an early stage. With CuZn-SOD KO mice, ZPP1 detected sub-RPE deposits at 10 months of age, whereas Zinpyr-1 required 14 months.CONCLUSION:
Detection of sub-RPE deposits by ZPP1 was greatly enhanced compared to Zinpyr-1. This enhanced sensitivity will allow for more insightful analysis of zinc in AMD using human specimens and mouse models. This could result in the development of a sensitive in-vivo probe to enhance research on the role zinc in drusen formation and the early clinical diagnosis of AMD.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Zinc
/
Epitelio Pigmentado de la Retina
/
Degeneración Macular Húmeda
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Trans Am Ophthalmol Soc
Año:
2017
Tipo del documento:
Article