Diabetologie und Stoffwechsel 2016; 11 - P82
DOI: 10.1055/s-0036-1580829

Clodronate treatment leads to microglial activation in degenerative retinopathy

S Riemann 1, M Kolibabka 1, N Gretz 2, S Hoffmann 2, S Busch 1, HP Hammes 1
  • 15th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
  • 2Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

Inflammation and glial activation can change the course of diabetic retinopathy (DR). The polycystic-kidney-disease (PKD)-rat shows a retinal phenotype similar to DR in which CD74 serves as a microglial activation marker. Our aim was to clarify the function of CD74+-microglia.

PKD-rats were intravitreally injected with clodronate-coated-liposomes at 4 and 8 weeks of age and terminated at 12 weeks. Clodronate-injected Sprague Dawley (SD)-rats served as control. Glial activation was assessed by immunofluorescence for activation markers. BV2-cells were stimulated towards M1 and M2 phenotypes and expression of activation markers was determined.

In the deep capillary layer clodronate-injected PKD-rats showed an increase of CD74+-microglia compared to uninjected animals (238 ± 70 vs. 69 ± 19 cells/mm2; p < 0.01) while the total number (Iba1+) remained unchanged (384 ± 38 vs. 295 ± 87cells/mm2; n.s.). In SD-rats, neither total (71 ± 40 vs. 30 ± 14 cells/mm2; n.s.) nor activated (17 ± 12 vs. 1 ± 1 cells/mm2; n.s.) microglia were elevated upon injection. In BV2-cells CD74 expression was increased in both, M1 (2.2-fold vs. control; p < 0.001) and M2 (2.6-fold vs. control; p < 0.0001). Glial activation was indicated by GFAP-positive Müller cells in clodronate-injected SD and PKD-rats.

Clodronate activates microglia. Since short-term application depletes microglia, our data on long-term effects indicates a stimulatory effect. The selective elevation and lack of polarization of CD74+-microglia is a basis for studies on the functional outcome.

Sponsored by GRK1874 (DIAMICOM) and DFG.