Abstract
Purpose :
The impact of chronic inflammation on the retina in the absence of inheritable/acquired disease or trauma has not been widely investigated. We have previously shown, in a mouse model of chronic neuroinflammation (GFAP-IL6), that the number of microglia found in the retina is increased in response to chronic inflammation. Here, we assessed the impact of chronic neuroinflammation on retinal neurons themselves. Further, we evaluated efficacy of oral Meriva curcumin as a potential neuroprotectant.
Methods :
The impact of inflammation on the retina was assessed by determining the length of the photoreceptor outer segments, thickness of outer nuclear layer (ONL) and inner nuclear layer (INL), and the density of cones. Heterozygous GFAP-IL6 mice (n=4), a model of chronic neuroinflammation, aged ~4 months were compared to their wild-type littermates (n=4). A separate cohort of GFAP-IL6 animals aged 4 months was treated with oral curcumin (n=5 ;140mg/kg) for 1 month (fed from 3 to 4 months) as a potential therapy to alleviate neuroinflammation.
Results :
Chronic IL6 expression was found to cause a significant decrease in ONL thickness when comparing WT to GFAP-IL6 retinal sections, suggesting a loss of photoreceptors. Indeed, a reduction in overall cone density (labelled with peanut agglutinin) was observed in GFAP-IL6 mice although M-cone density (labelled with M-opsin) was unchanged suggesting S-cones are preferentially affected by chronic neuroinflammation. While rod photoreceptors may have been lost, no significant differences were seen in rod outer segment length between genotypes. There was a trend of reduced INL thickness, but this was not statistically significant. No obvious GFAP expression was observed in Müller cells in any group. However, significant GFAP staining could be found in astrocytes residing outside the inner limiting membrane although no obvious difference could be seen between groups. In the Meriva curcumin treated animals, both cone density and ONL thickness were indistinguishable from wild-types suggesting a significant neuroprotective effect.
Conclusions :
Chronic inflammation leads to a reduction in cell bodies in the ONL as well as a reduction in cone density. Our results indicate that curcumin supplementation can protect the retina from these harmful effects of chronic neuroinflammation and may be a candidate to improve outcomes in patients with degenerative retinal disease.
This is a 2021 ARVO Annual Meeting abstract.