CD74 indicates microglial activation in experimental diabetic retinopathy and exogenous methylglyoxal mimics the
Jing Wang1, Jihong Lin, Andreas Schlotterer
15th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
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.
Insights
Advanced glycation end products (AGEs) like methylglyoxal increase CD74 expression in retinal microglia, indicating microglial activation in diabetic retinopathy.
Area of Science:
- Ophthalmology
- Neuroscience
- Endocrinology
Background:
- Diabetes mellitus causes retinal damage, including neurodegeneration and glial cell activation.
- Advanced glycation end products (AGEs) accumulate in diabetes and contribute to diabetic retinopathy pathogenesis.
- CD74 expression is elevated in activated microglia in diabetic rat models.
Purpose of the Study:
- To investigate if glucose and methylglyoxal (a major AGE precursor) increase CD74 expression in the retina.
- To identify CD74 as a potential marker for microglial activation in diabetic retinopathy.
Main Methods:
- Retinal microglia CD74 expression was analyzed in streptozotocin-induced diabetic rats using wholemount immunofluorescence.
- Nondiabetic mice received intravitreal injections of methylglyoxal, with CD74 expression assessed via immunofluorescence and quantitative real-time PCR 48 hours post-injection.
Main Results:
- Diabetic rats showed a significant increase in CD74-positive cells within the superficial vascular layer of the retina, primarily within a subpopulation of activated microglia (13.7-fold increase).
- Methylglyoxal injection in mice led to a 9.4-fold increase in CD74-positive cells in the superficial vascular layer and a 2.8-fold elevation in retinal CD74 gene expression.
Conclusions:
- CD74 serves as a marker for microglial activation in the diabetic retina.
- Exogenous methylglyoxal administration effectively mimics the observed CD74 upregulation in normoglycemic retinas.
- Methylglyoxal plays a significant role in mediating microglial activation within the context of diabetic retinopathy.
