Abstract
Purpose :
Neuroinflammation is thought to play a substantive role in many degenerative eye disorders, including macular degeneration, diabetic retinopathy, glaucoma, retinal vein occlusion and retinitis pigmentosa. The purpose of this study was to examine retinal microglia in a mouse model of chronic neuroinflammation induced by astroglia-specific production of interleukin 6 (GFAP-IL6). Furthermore, we aimed to determine the effect of increasing doses of highly bioavailable curcumin on microglial changes in response to chronic inflammation.
Methods :
Four month old heterozygous GFAP-IL6 mice were fed different doses (0, 35, 70 and 140mg/kg per day) of highly bioavailable curcumin for one month and compared to unfed wild-type littermates (n=5 mice each group). Whole mount retinae were stained for microglia specific antigen Iba-1. Microglial density was determined by counting > 2000 cells per retina. 3D reconstruction and morphological analysis were performed using Neurolucida software (n=100 cells each group).
Results :
GFAP-IL6 showed a significant increase in microglia density when compared against wild-type retinae. This increase can be completely reversed by the highest dose of bioavailable curcumin (140mg/kg) with lower doses reducing microglial numbers in a dose-dependent manner. Several changes in the morphology of microglia in GFAP-IL6 mice were observed, including a significant decrease in convex hull area (6500 to 4500 µm2) and a significant increase in soma area (50 to 60 µm2). However, these changes cannot be reversed to wild-type levels with any dosage of curcumin. Furthermore, Sholl analysis reveals a shift in dendritic complexity towards the soma when mice are treated with curcumin.
Conclusions :
Microglial density is significantly upregulated in the GFAP-IL6 retinae in comparison to littermate wild-type controls, with morphological changes indicative of microglial activation. Curcumin feeding caused a dose-dependent reduction in microglial density in the GFAP-IL6 mice as well as a trend to cause dendritic retraction at any dosage.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.