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Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration
Age-related macular degeneration is the leading cause of blindness in the developed world. Since advanced glycation end products (AGEs) are implicated in the pathogenesis of AMD through various lines of evidence, we investigated the potential of fructosamine-3-kinase (FN3K) in the disruption of reti...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565857/ https://www.ncbi.nlm.nih.gov/pubmed/32899850 http://dx.doi.org/10.3390/jcm9092869 |
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author | De Bruyne, Sander Van den Broecke, Caroline Vrielinck, Henk Khelifi, Samira De Wever, Olivier Bracke, Ken Huizing, Manon Boston, Nezahat Himpe, Jonas Speeckaert, Marijn Vral, Anne Van Dorpe, Jo Van Aken, Elisabeth Delanghe, Joris R. |
author_facet | De Bruyne, Sander Van den Broecke, Caroline Vrielinck, Henk Khelifi, Samira De Wever, Olivier Bracke, Ken Huizing, Manon Boston, Nezahat Himpe, Jonas Speeckaert, Marijn Vral, Anne Van Dorpe, Jo Van Aken, Elisabeth Delanghe, Joris R. |
author_sort | De Bruyne, Sander |
collection | PubMed |
description | Age-related macular degeneration is the leading cause of blindness in the developed world. Since advanced glycation end products (AGEs) are implicated in the pathogenesis of AMD through various lines of evidence, we investigated the potential of fructosamine-3-kinase (FN3K) in the disruption of retinal AGEs, drusenoid material and drusenoid lesions in patients with AMD. AGE-type autofluorescence was measured to evaluate the effects of FN3K on glycolaldehyde-induced AGE-modified neural porcine retinas and unmodified human neural retinas. Eye pairs from cigarette-smoke- and air-exposed mice were treated and evaluated histologically. Automated optical image analysis of human tissue sections was performed to compare control- and FN3K-treated drusen and near-infrared (NIR) microspectroscopy was performed to examine biochemical differences. Optical coherence tomography (OCT) was used to evaluate the effect of FN3K on drusenoid deposits after treatment of post-mortem human eyes. FN3K treatment provoked a significant decrease (41%) of AGE-related autofluorescence in the AGE-modified porcine retinas. Furthermore, treatment of human neural retinas resulted in significant decreases of autofluorescence (−24%). FN3K-treated murine eyes showed less drusenoid material. Pairwise comparison of drusen on tissue sections revealed significant changes in color intensity after FN3K treatment. NIR microspectroscopy uncovered clear spectral differences in drusenoid material (Bruch’s membrane) and drusen after FN3K treatment. Ex vivo treatment strongly reduced size of subretinal drusenoid lesions on OCT imaging (up to 83%). In conclusion, our study demonstrated for the first time a potential role of FN3K in the disruption of AGE-related retinal autofluorescence, drusenoid material and drusenoid lesions in patients with AMD. |
format | Online Article Text |
id | pubmed-7565857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75658572020-10-26 Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration De Bruyne, Sander Van den Broecke, Caroline Vrielinck, Henk Khelifi, Samira De Wever, Olivier Bracke, Ken Huizing, Manon Boston, Nezahat Himpe, Jonas Speeckaert, Marijn Vral, Anne Van Dorpe, Jo Van Aken, Elisabeth Delanghe, Joris R. J Clin Med Article Age-related macular degeneration is the leading cause of blindness in the developed world. Since advanced glycation end products (AGEs) are implicated in the pathogenesis of AMD through various lines of evidence, we investigated the potential of fructosamine-3-kinase (FN3K) in the disruption of retinal AGEs, drusenoid material and drusenoid lesions in patients with AMD. AGE-type autofluorescence was measured to evaluate the effects of FN3K on glycolaldehyde-induced AGE-modified neural porcine retinas and unmodified human neural retinas. Eye pairs from cigarette-smoke- and air-exposed mice were treated and evaluated histologically. Automated optical image analysis of human tissue sections was performed to compare control- and FN3K-treated drusen and near-infrared (NIR) microspectroscopy was performed to examine biochemical differences. Optical coherence tomography (OCT) was used to evaluate the effect of FN3K on drusenoid deposits after treatment of post-mortem human eyes. FN3K treatment provoked a significant decrease (41%) of AGE-related autofluorescence in the AGE-modified porcine retinas. Furthermore, treatment of human neural retinas resulted in significant decreases of autofluorescence (−24%). FN3K-treated murine eyes showed less drusenoid material. Pairwise comparison of drusen on tissue sections revealed significant changes in color intensity after FN3K treatment. NIR microspectroscopy uncovered clear spectral differences in drusenoid material (Bruch’s membrane) and drusen after FN3K treatment. Ex vivo treatment strongly reduced size of subretinal drusenoid lesions on OCT imaging (up to 83%). In conclusion, our study demonstrated for the first time a potential role of FN3K in the disruption of AGE-related retinal autofluorescence, drusenoid material and drusenoid lesions in patients with AMD. MDPI 2020-09-04 /pmc/articles/PMC7565857/ /pubmed/32899850 http://dx.doi.org/10.3390/jcm9092869 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article De Bruyne, Sander Van den Broecke, Caroline Vrielinck, Henk Khelifi, Samira De Wever, Olivier Bracke, Ken Huizing, Manon Boston, Nezahat Himpe, Jonas Speeckaert, Marijn Vral, Anne Van Dorpe, Jo Van Aken, Elisabeth Delanghe, Joris R. Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration |
title | Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration |
title_full | Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration |
title_fullStr | Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration |
title_full_unstemmed | Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration |
title_short | Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration |
title_sort | fructosamine-3-kinase as a potential treatment option for age-related macular degeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565857/ https://www.ncbi.nlm.nih.gov/pubmed/32899850 http://dx.doi.org/10.3390/jcm9092869 |
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