title: CD74 indicates microglial activation in experimental diabetic retinopathy and exogenous methylglyoxal mimics the response in normoglycemic retina.
abstract: Diabetes induces vasoregression, neurodegeneration and glial activation in the retina. Formation of advanced glycation endoproducts (AGEs) is increased in diabetes and contributes to the pathogenesis of diabetic retinopathy. CD74 is increased in activated microglia in a rat model developing both neurodegeneration and vasoregression. In this study, we aimed at investigating whether glucose and major AGE precursor methylglyoxal induce increased CD74 expression in the retina. Expression of CD74 in retinal microglia was analyzed in streptozotocin-diabetic rats by wholemount immunofluorescence. Nondiabetic mice were intravitreally injected with methylglyoxal. Expression of CD74 was studied by retinal wholemount immunofluorescence and quantitative real-time PCR, 48 h after the injection. CD74-positive cells were increased in diabetic 4-month retinas. These cells represented a subpopulation of CD11b-labeled activated microglia and were mainly located in the superficial vascular layer (13.7-fold increase compared to nondiabetic group). Methylglyoxal induced an 9.4-fold increase of CD74-positive cells in the superficial vascular layer and elevated gene expression of CD74 in the mouse retina 2.8-fold. In summary, we identified CD74 as a microglial activation marker in the diabetic retina. Exogenous methylglyoxal mimics the response in normoglycemic retina. This suggests that methylglyoxal is important in mediating microglial activation in the diabetic retina.
authors: 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
authors: Jing
authors: J
authors: Wang
authors: Jihong
authors: J
authors: Lin
authors: Andreas
authors: A
authors: Schlotterer
authors: Liang
authors: L
authors: Wu
authors: Thomas
authors: T
authors: Fleming
authors: Stephanie
authors: S
authors: Busch
authors: Nadine
authors: N
authors: Dietrich
authors: Hans-Peter
authors: HP
authors: Hammes
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D018845:CD11 Antigens / Q000235:genetics / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D018845:CD11 Antigens; D017127:Glycation End Products, Advanced; D000949:Histocompatibility Antigens Class II; C045084:invariant chain; D011765:Pyruvaldehyde; D005947:Glucose