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Serine racemase deletion attenuates neurodegeneration and microvascular damage in diabetic retinopathy

Diabetic retinopathy (DR) is a leading cause of blindness. DR is recognized as a microvascular disease and inner retinal neurodegeneration. In the course of retinal neurodegeneration, N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity is involved. Full activation of NMDAR requires binding...

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Autores principales: Ozaki, Hironori, Inoue, Ran, Matsushima, Takako, Sasahara, Masakiyo, Hayashi, Atsushi, Mori, Hisashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755926/
https://www.ncbi.nlm.nih.gov/pubmed/29304076
http://dx.doi.org/10.1371/journal.pone.0190864
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author Ozaki, Hironori
Inoue, Ran
Matsushima, Takako
Sasahara, Masakiyo
Hayashi, Atsushi
Mori, Hisashi
author_facet Ozaki, Hironori
Inoue, Ran
Matsushima, Takako
Sasahara, Masakiyo
Hayashi, Atsushi
Mori, Hisashi
author_sort Ozaki, Hironori
collection PubMed
description Diabetic retinopathy (DR) is a leading cause of blindness. DR is recognized as a microvascular disease and inner retinal neurodegeneration. In the course of retinal neurodegeneration, N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity is involved. Full activation of NMDAR requires binding of agonist glutamate and coagonist glycine or D-serine. D-Serine is produced from L-serine by serine racemase (SRR) and contributes to retinal neurodegeneration in rodent models of DR. However, the involvement of SRR in both neurodegeneration and microvascular damage in DR remains unclear. Here, we established diabetic model of SRR knockout (SRR-KO) and control wild-type (WT) mice by streptozotocin injection. Six months after the onset of diabetes, the number of survived retinal ganglion cells was higher in SRR-KO mice than that of WT mice. The reduction of thickness of inner retinal layer (IRL) was attenuated in SRR-KO mice than that of WT mice. Moreover, the number of damaged acellular capillaries was lower in SRR-KO mice than that of WT mice. Our results suggest the suppression of SRR activity may have protective effects in DR.
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spelling pubmed-57559262018-01-26 Serine racemase deletion attenuates neurodegeneration and microvascular damage in diabetic retinopathy Ozaki, Hironori Inoue, Ran Matsushima, Takako Sasahara, Masakiyo Hayashi, Atsushi Mori, Hisashi PLoS One Research Article Diabetic retinopathy (DR) is a leading cause of blindness. DR is recognized as a microvascular disease and inner retinal neurodegeneration. In the course of retinal neurodegeneration, N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity is involved. Full activation of NMDAR requires binding of agonist glutamate and coagonist glycine or D-serine. D-Serine is produced from L-serine by serine racemase (SRR) and contributes to retinal neurodegeneration in rodent models of DR. However, the involvement of SRR in both neurodegeneration and microvascular damage in DR remains unclear. Here, we established diabetic model of SRR knockout (SRR-KO) and control wild-type (WT) mice by streptozotocin injection. Six months after the onset of diabetes, the number of survived retinal ganglion cells was higher in SRR-KO mice than that of WT mice. The reduction of thickness of inner retinal layer (IRL) was attenuated in SRR-KO mice than that of WT mice. Moreover, the number of damaged acellular capillaries was lower in SRR-KO mice than that of WT mice. Our results suggest the suppression of SRR activity may have protective effects in DR. Public Library of Science 2018-01-05 /pmc/articles/PMC5755926/ /pubmed/29304076 http://dx.doi.org/10.1371/journal.pone.0190864 Text en © 2018 Ozaki et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ozaki, Hironori
Inoue, Ran
Matsushima, Takako
Sasahara, Masakiyo
Hayashi, Atsushi
Mori, Hisashi
Serine racemase deletion attenuates neurodegeneration and microvascular damage in diabetic retinopathy
title Serine racemase deletion attenuates neurodegeneration and microvascular damage in diabetic retinopathy
title_full Serine racemase deletion attenuates neurodegeneration and microvascular damage in diabetic retinopathy
title_fullStr Serine racemase deletion attenuates neurodegeneration and microvascular damage in diabetic retinopathy
title_full_unstemmed Serine racemase deletion attenuates neurodegeneration and microvascular damage in diabetic retinopathy
title_short Serine racemase deletion attenuates neurodegeneration and microvascular damage in diabetic retinopathy
title_sort serine racemase deletion attenuates neurodegeneration and microvascular damage in diabetic retinopathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755926/
https://www.ncbi.nlm.nih.gov/pubmed/29304076
http://dx.doi.org/10.1371/journal.pone.0190864
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