Abstract
Purpose :
Glucagon-like peptide-1 (GLP1)is an incretin hormone that primarily work on βcells in the pancreas, but extrapancreatic action of GLP1 such as anti-inflamation and neuroprotection is reported recently. In the present study, we investigate the effect of GLP1 on choroidal neovascularization (CNV) in a mouse model.
Methods :
We treated 6-week-old C57BL/6J mice with laser and induced CNV. Expression of GLP1 receptor was assessed with immunohistochemistry. We administered liraglutide subcutaneously once per day and compared the size of CNV with control. To investigate whether the effect is mediated by intraocular GLP1 receptor, GLP1 antagonist was administered intravitreally. cDNA was collected from retinal pigment epithelium/choroid/sclera at day 1, 3, and 7. Expression of GLP1 and inflammatory cytokines were investigated.
Results :
Expression of GLP1 receptor was noted in retinal ganglion cells, cells in the inner nuclear layer, outer nuclear layer, and retinal pigment epithelium. Administration of liraglutide 250, 500, 1000 μg/kg reduced the CNV size to 15341, 13232, 11491 μm2,, respectively, compared to control 20080 μm2. The inhibitory effect was cancelled with intravitreal injection of GLP1 antagonist exendin3. While laser treatment promoted expression of NLRP3, IL1β, IL6, and TNFα, the expression level was reduced by GLP1 treatment (NLRP3 2.6 folds to 1.5 folds, IL1β 5.3 folds to 3.1 folds, IL6 15.3 folds to 5.2 folds, and TNFα 1.8 folds to 1.0 fold at day 1, respectively).
Conclusions :
GLP1 inhibits CNV formation via intraocular GLP1 receptor. Inhibition of inflammatory process including NLRP3 was considered as the mechanism of action.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.