期刊
EXPERIMENTAL EYE RESEARCH
卷 175, 期 -, 页码 90-97出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2018.06.017
关键词
Diabetic retinopathy; Retinal ganglion cell; Retinal degeneration; D-serine; Retinal ganglion cell; Ins2(Akita)
资金
- National Natural Science Foundation of China [81371027]
- Zhejiang Province Natural Science Foundation [LY18H120003]
- National Natural Science Foundation of China for youth [81600755]
- Wenzhou Medical University [QTJ10 001]
Consistent results suggest the promoting roles of serine racemase (SR)/D-serine in retinal neurodegeneration in diabetic retinopathy (DR). However, the direct evidence connecting SR deficiency with retinal neuroprotection in genetic model of diabetes mellitus has not been reported. In this investigation, we explore the effect of absence of functional SR on the degeneration of retinal ganglion cells (RGCs) with a diabetic murine model, Ins2(Akita) mice. We established a murine strain with double mutation, termed Ins2(Akita)-Srr, by mating heterozygous Ins2(Akita) mice with homozygous Srethre269 mice. Ins2(Akita) retained less RGC in posterior, middle, and peripheral retinae than the counterpart from non-diabetic sibling mice at the age of five or seven months. Ins2(Akita)-Srr mice retained more RGC in middle and peripheral but not in posterior retinae than the counterpart from Ins2(Akita) sibling mice at the age of five months. By contrast, at the age of seven months, Ins2(Akita)-.Srr mice contained more RGC in peripheral, middle, and posterior retinae than the counterpart from Ins2(Akita). RGCs were identified with retrograde labeling in vivo or with immunolabeling against a RGC-specific transcription factor, Bm3a, in retinal fiat mounts. Correspondingly, the aqueous humor of Ins2(Akita)-Srr contained less amount of D-serine than sibling Ins2(Akita) mice. Thus, SR deficiency significantly prevented RGC loss in diabetic mice. We conclude that D-serine is a critical factor in the degeneration of RGC in DR. Targeting SR expression or activity may be a strategy for ameliorating RGC loss in DR.
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