title: Overexpression of serine racemase in retina and overproduction of D-serine in eyes of streptozotocin-induced diabetic retinopathy.
abstract: BACKGROUND
  Recent data indicate that inflammatory mechanisms contribute to diabetic retinopathy (DR). We have determined that serine racemase (SR) expression is increased by inflammatory stimuli including liposaccharide (LPS), amyloid β-peptide (A-beta), and secreted amyloid precursor protein (sAPP); expression is decreased by the anti-inflammatory drug, dexamethasone. We tested possibility that SR and its product, D-serine, were altered in a rat model of DR.
  
  
  METHODS
  Intraperitoneal injection of streptozotocin (STZ; 70 mg/kg body weight) to Sprague-Dawley rats produced type-I diabetic mellitus (fasting blood sugar higher than 300 mg/dL). At 3 and 5 months after STZ or saline injection, retinas from some rats were subjected to cryosectioning for immunofluorescent analysis of SR and TUNEL assay of apoptosis. Retinal homogenates were used to detect SR levels and Jun N-terminal kinase (JNK) activation by immunoblotting. Aqueous humor and retina were also collected to assay for neurotransmitters, including glutamate and D-serine, by reverse-phase HPLC.
  
  
  RESULTS
  Compared to saline-injected rats, STZ-injected (diabetic) rats showed elevation of SR protein levels in retinal homogenates, attributed to the inner nuclear layer (INL) by immunofluorescence. Aqueous humor fluid from STZ-injected rats contained significantly higher levels of glutamate and D-serine compared to controls; by contrast, D-serine levels in retinas did not differ. Levels of activated JNK were elevated in diabetic retinas compared to controls.
  
  
  CONCLUSIONS
  Increased expression of SR in retina and higher levels of glutamate and D-serine in aqueous humor of STZ-treated rats may result from activation of the JNK pathway in diabetic sequelae. Our data suggest that the inflammatory conditions that prevail during DR result in elevation of D-serine, a neurotransmitter contributing to glutamate toxicity, potentially exacerbating the death of retinal ganglion cells in this condition.
authors.affiliation: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, 270 Xueyuan Road, Wenzhou, Zhejiang 325003, P.R. China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jiang
authors.forename: Junxu
authors.initials: J
authors.lastname: Fang
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.forename: Guibin
authors.initials: G
authors.lastname: Yin
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.forename: Steven W
authors.initials: SW
authors.lastname: Barger
authors.forename: Shengzhou
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D016923:Cell Death; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D019998:Racemases and Epimerases / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000201:enzymology*; D012694:Serine / Q000737:chemistry / Q000378:metabolism*; D013311:Streptozocin; D000099300:Serine Racemase
chemical_list: D001786:Blood Glucose; D018698:Glutamic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D019998:Racemases and Epimerases; D012694:Serine; D013311:Streptozocin; D000099300:Serine Racemase