Differential Responses of Neural Retina Progenitor Populations to Chronic Hyperglycemia

Diabetic retinopathy is a frequent complication of longstanding diabetes, which comprises a complex interplay of microvascular abnormalities and neurodegeneration. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor <i>pdx1</i> display a diabetic phenotype wi...

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Autores principales:	Nicole Schmitner, Christina Recheis, Jakob Thönig, Robin A. Kimmel
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	retinal degeneration regeneration progenitor cell diabetes hyperglycemia photoreceptors Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6248533927c34a59873abc4f19176d45
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spelling	oai:doaj.org-article:6248533927c34a59873abc4f19176d452021-11-25T17:13:26ZDifferential Responses of Neural Retina Progenitor Populations to Chronic Hyperglycemia10.3390/cells101132652073-4409https://doaj.org/article/6248533927c34a59873abc4f19176d452021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3265https://doaj.org/toc/2073-4409Diabetic retinopathy is a frequent complication of longstanding diabetes, which comprises a complex interplay of microvascular abnormalities and neurodegeneration. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor <i>pdx1</i> display a diabetic phenotype with survival into adulthood, and are therefore uniquely suitable among zebrafish models for studying pathologies associated with persistent diabetic conditions. We have previously shown that, starting at three months of age, <i>pdx1</i> mutants exhibit not only vascular but also neuro-retinal pathologies manifesting as photoreceptor dysfunction and loss, similar to human diabetic retinopathy. Here, we further characterize injury and regenerative responses and examine the effects on progenitor cell populations. Consistent with a negative impact of hyperglycemia on neurogenesis, stem cells of the ciliary marginal zone show an exacerbation of aging-related proliferative decline. In contrast to the robust Müller glial cell proliferation seen following acute retinal injury, the <i>pdx1</i> mutant shows replenishment of both rod and cone photoreceptors from slow-cycling, neurod-expressing progenitors which first accumulate in the inner nuclear layer. Overall, we demonstrate a diabetic retinopathy model which shows pathological features of the human disease evolving alongside an ongoing restorative process that replaces lost photoreceptors, at the same time suggesting an unappreciated phenotypic continuum between multipotent and photoreceptor-committed progenitors.Nicole SchmitnerChristina RecheisJakob ThönigRobin A. KimmelMDPI AGarticleretinal degenerationregenerationprogenitor celldiabeteshyperglycemiaphotoreceptorsBiology (General)QH301-705.5ENCells, Vol 10, Iss 3265, p 3265 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	retinal degeneration regeneration progenitor cell diabetes hyperglycemia photoreceptors Biology (General) QH301-705.5
spellingShingle	retinal degeneration regeneration progenitor cell diabetes hyperglycemia photoreceptors Biology (General) QH301-705.5 Nicole Schmitner Christina Recheis Jakob Thönig Robin A. Kimmel Differential Responses of Neural Retina Progenitor Populations to Chronic Hyperglycemia
description	Diabetic retinopathy is a frequent complication of longstanding diabetes, which comprises a complex interplay of microvascular abnormalities and neurodegeneration. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor <i>pdx1</i> display a diabetic phenotype with survival into adulthood, and are therefore uniquely suitable among zebrafish models for studying pathologies associated with persistent diabetic conditions. We have previously shown that, starting at three months of age, <i>pdx1</i> mutants exhibit not only vascular but also neuro-retinal pathologies manifesting as photoreceptor dysfunction and loss, similar to human diabetic retinopathy. Here, we further characterize injury and regenerative responses and examine the effects on progenitor cell populations. Consistent with a negative impact of hyperglycemia on neurogenesis, stem cells of the ciliary marginal zone show an exacerbation of aging-related proliferative decline. In contrast to the robust Müller glial cell proliferation seen following acute retinal injury, the <i>pdx1</i> mutant shows replenishment of both rod and cone photoreceptors from slow-cycling, neurod-expressing progenitors which first accumulate in the inner nuclear layer. Overall, we demonstrate a diabetic retinopathy model which shows pathological features of the human disease evolving alongside an ongoing restorative process that replaces lost photoreceptors, at the same time suggesting an unappreciated phenotypic continuum between multipotent and photoreceptor-committed progenitors.
format	article
author	Nicole Schmitner Christina Recheis Jakob Thönig Robin A. Kimmel
author_facet	Nicole Schmitner Christina Recheis Jakob Thönig Robin A. Kimmel
author_sort	Nicole Schmitner
title	Differential Responses of Neural Retina Progenitor Populations to Chronic Hyperglycemia
title_short	Differential Responses of Neural Retina Progenitor Populations to Chronic Hyperglycemia
title_full	Differential Responses of Neural Retina Progenitor Populations to Chronic Hyperglycemia
title_fullStr	Differential Responses of Neural Retina Progenitor Populations to Chronic Hyperglycemia
title_full_unstemmed	Differential Responses of Neural Retina Progenitor Populations to Chronic Hyperglycemia
title_sort	differential responses of neural retina progenitor populations to chronic hyperglycemia
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6248533927c34a59873abc4f19176d45
work_keys_str_mv	AT nicoleschmitner differentialresponsesofneuralretinaprogenitorpopulationstochronichyperglycemia AT christinarecheis differentialresponsesofneuralretinaprogenitorpopulationstochronichyperglycemia AT jakobthonig differentialresponsesofneuralretinaprogenitorpopulationstochronichyperglycemia AT robinakimmel differentialresponsesofneuralretinaprogenitorpopulationstochronichyperglycemia
_version_	1718412591702736896

Differential Responses of Neural Retina Progenitor Populations to Chronic Hyperglycemia

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