Serine racemase deletion attenuates neurodegeneration and microvascular damage in diabetic retinopathy

PloS One
Hironori OzakiHisashi Mori

Abstract

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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Citations

Jul 26, 2019·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Laurits J Holm, Karsten Buschard
Apr 24, 2020·Diabetes·Bruce A CorlissShayn M Peirce
Oct 27, 2018·Mediators of Inflammation·Sebastián Beltrán-CastilloRommy von Bernhardi
Jun 22, 2021·Journal of Diabetes Research·Shani PillarAndrzej Grzybowski
Aug 11, 2021·Experimental and Therapeutic Medicine·Xiaoyu LiXiang Ren

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Methods Mentioned

BETA
Protein Assay

Software Mentioned

MetaMorph

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