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Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock

The present epidemic of diabetes is resulting in a worldwide increase in cardiovascular and microvascular complications including retinopathy. Current thinking has focused on local influences in the retina as being responsible for development of this diabetic complication. However, the contribution...

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Autores principales: Busik, Julia V., Tikhonenko, Maria, Bhatwadekar, Ashay, Opreanu, Madalina, Yakubova, Nafissa, Caballero, Sergio, Player, Danny, Nakagawa, Takahiko, Afzal, Aqeela, Kielczewski, Jennifer, Sochacki, Andrew, Hasty, Stephanie, Calzi, Sergio Li, Kim, Sungjin, Duclas, Shane K., Segal, Mark S., Guberski, Dennis L., Esselman, Walter J., Boulton, Michael E., Grant, Maria B.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806461/
https://www.ncbi.nlm.nih.gov/pubmed/19934019
http://dx.doi.org/10.1084/jem.20090889
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author Busik, Julia V.
Tikhonenko, Maria
Bhatwadekar, Ashay
Opreanu, Madalina
Yakubova, Nafissa
Caballero, Sergio
Player, Danny
Nakagawa, Takahiko
Afzal, Aqeela
Kielczewski, Jennifer
Sochacki, Andrew
Hasty, Stephanie
Calzi, Sergio Li
Kim, Sungjin
Duclas, Shane K.
Segal, Mark S.
Guberski, Dennis L.
Esselman, Walter J.
Boulton, Michael E.
Grant, Maria B.
author_facet Busik, Julia V.
Tikhonenko, Maria
Bhatwadekar, Ashay
Opreanu, Madalina
Yakubova, Nafissa
Caballero, Sergio
Player, Danny
Nakagawa, Takahiko
Afzal, Aqeela
Kielczewski, Jennifer
Sochacki, Andrew
Hasty, Stephanie
Calzi, Sergio Li
Kim, Sungjin
Duclas, Shane K.
Segal, Mark S.
Guberski, Dennis L.
Esselman, Walter J.
Boulton, Michael E.
Grant, Maria B.
author_sort Busik, Julia V.
collection PubMed
description The present epidemic of diabetes is resulting in a worldwide increase in cardiovascular and microvascular complications including retinopathy. Current thinking has focused on local influences in the retina as being responsible for development of this diabetic complication. However, the contribution of circulating cells in maintenance, repair, and dysfunction of the vasculature is now becoming appreciated. Diabetic individuals have fewer endothelial progenitor cells (EPCs) in their circulation and these cells have diminished migratory potential, which contributes to their decreased reparative capacity. Using a rat model of type 2 diabetes, we show that the decrease in EPC release from diabetic bone marrow is caused by bone marrow neuropathy and that these changes precede the development of diabetic retinopathy. In rats that had diabetes for 4 mo, we observed a dramatic reduction in the number of nerve terminal endings in the bone marrow. Denervation was accompanied by increased numbers of EPCs within the bone marrow but decreased numbers in circulation. Furthermore, denervation was accompanied by a loss of circadian release of EPCs and a marked reduction in clock gene expression in the retina and in EPCs themselves. This reduction in the circadian peak of EPC release led to diminished reparative capacity, resulting in the development of the hallmark feature of diabetic retinopathy, acellular retinal capillaries. Thus, for the first time, diabetic retinopathy is related to neuropathy of the bone marrow. This novel finding shows that bone marrow denervation represents a new therapeutic target for treatment of diabetic vascular complications.
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spelling pubmed-28064612010-06-21 Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock Busik, Julia V. Tikhonenko, Maria Bhatwadekar, Ashay Opreanu, Madalina Yakubova, Nafissa Caballero, Sergio Player, Danny Nakagawa, Takahiko Afzal, Aqeela Kielczewski, Jennifer Sochacki, Andrew Hasty, Stephanie Calzi, Sergio Li Kim, Sungjin Duclas, Shane K. Segal, Mark S. Guberski, Dennis L. Esselman, Walter J. Boulton, Michael E. Grant, Maria B. J Exp Med Brief Definitive Report The present epidemic of diabetes is resulting in a worldwide increase in cardiovascular and microvascular complications including retinopathy. Current thinking has focused on local influences in the retina as being responsible for development of this diabetic complication. However, the contribution of circulating cells in maintenance, repair, and dysfunction of the vasculature is now becoming appreciated. Diabetic individuals have fewer endothelial progenitor cells (EPCs) in their circulation and these cells have diminished migratory potential, which contributes to their decreased reparative capacity. Using a rat model of type 2 diabetes, we show that the decrease in EPC release from diabetic bone marrow is caused by bone marrow neuropathy and that these changes precede the development of diabetic retinopathy. In rats that had diabetes for 4 mo, we observed a dramatic reduction in the number of nerve terminal endings in the bone marrow. Denervation was accompanied by increased numbers of EPCs within the bone marrow but decreased numbers in circulation. Furthermore, denervation was accompanied by a loss of circadian release of EPCs and a marked reduction in clock gene expression in the retina and in EPCs themselves. This reduction in the circadian peak of EPC release led to diminished reparative capacity, resulting in the development of the hallmark feature of diabetic retinopathy, acellular retinal capillaries. Thus, for the first time, diabetic retinopathy is related to neuropathy of the bone marrow. This novel finding shows that bone marrow denervation represents a new therapeutic target for treatment of diabetic vascular complications. The Rockefeller University Press 2009-12-21 /pmc/articles/PMC2806461/ /pubmed/19934019 http://dx.doi.org/10.1084/jem.20090889 Text en © 2009 Busik et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Busik, Julia V.
Tikhonenko, Maria
Bhatwadekar, Ashay
Opreanu, Madalina
Yakubova, Nafissa
Caballero, Sergio
Player, Danny
Nakagawa, Takahiko
Afzal, Aqeela
Kielczewski, Jennifer
Sochacki, Andrew
Hasty, Stephanie
Calzi, Sergio Li
Kim, Sungjin
Duclas, Shane K.
Segal, Mark S.
Guberski, Dennis L.
Esselman, Walter J.
Boulton, Michael E.
Grant, Maria B.
Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock
title Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock
title_full Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock
title_fullStr Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock
title_full_unstemmed Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock
title_short Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock
title_sort diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806461/
https://www.ncbi.nlm.nih.gov/pubmed/19934019
http://dx.doi.org/10.1084/jem.20090889
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