RRC ID 53174
Author Jiang H, Du J, Song J, Li Y, Wu M, Zhou J, Wu S.
Title Loss-of-function mutation of serine racemase attenuates retinal ganglion cell loss in diabetic mice.
Journal Exp Eye Res
Abstract 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, Ins2Akita mice. We established a murine strain with double mutation, termed Ins2Akita-Srr, by mating heterozygous Ins2Akita mice with homozygous Srrochre269 mice. Ins2Akita 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. Ins2Akita-Srr mice retained more RGC in middle and peripheral--but not in posterior-- retinae than the counterpart from Ins2Akita sibling mice at the age of five months. By contrast, at the age of seven months, Ins2Akita-Srr mice contained more RGC in peripheral, middle, and posterior retinae than the counterpart from Ins2Akita. RGCs were identified with retrograde labeling in vivo or with immunolabeling against a RGC-specific transcription factor, Brn3a, in retinal flat mounts. Correspondingly, the aqueous humor of Ins2Akita-Srr contained less amount of D-serine than sibling Ins2Akita 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.
Volume 175
Pages 90-97
Published 2018-10-1
DOI 10.1016/j.exer.2018.06.017
PII S0014-4835(17)30792-3
PMID 29913163
MeSH Animals Blood Glucose / metabolism Cell Count Diabetes Mellitus, Experimental / metabolism Diabetes Mellitus, Experimental / pathology Diabetes Mellitus, Experimental / prevention & control Diabetic Retinopathy / metabolism Diabetic Retinopathy / pathology Diabetic Retinopathy / prevention & control* Disease Models, Animal* Fluorescent Antibody Technique, Indirect Genotyping Techniques Hyperglycemia / metabolism Hyperglycemia / pathology In Situ Nick-End Labeling Insulin / genetics Loss of Function Mutation / genetics* Mice Mice, Inbred C57BL Microscopy, Fluorescence Polymerase Chain Reaction Racemases and Epimerases / genetics* Retinal Degeneration / metabolism Retinal Degeneration / prevention & control* Retinal Ganglion Cells / metabolism* Retinal Ganglion Cells / pathology
IF 3.011
Times Cited 4
Mice RBRCGD000099