Abstract
Purpose :
Glucagon-like peptide 1 receptor (GLP-1R) agonists have been found to be vasculoprotective and anti-inflammatory in multiple disease models, such as cardiac and retinal ischemia reperfusion, but its role in retinal angiogenesis remains unclear. This study investigated whether NLY01, a long acting GLP-1R agonist could promote re-vascularization of the retinal vasculature and ameliorate pathologic retinal neovascularization in the oxygen-induced retinopathy (OIR) model
Methods :
C57BL/6J mouse pups were placed in 75 ± 2% oxygen from postnatal day 7 (P7) to P12. After returning back to room air at P12, pups received intravitreal injection of NLY01 or NLY01-FITC in one eye. The contralateral eyes were injected with PBS as control. The avascular and neovascular area was assessed by lectin staining at P17. The expression of GLP-1R was evaluated in cryosections from both room air and OIR retinas. The localization of NLY01-FITC in retina was visualized by flatmounting and staining of P13, P15 and P17 OIR retinas. To illustrate the anti-inflammatory effect of NLY01, BV-2 microglial cells were pretreated with NLY01 and then incubated with LPS. Cells were harvested for evaluation of inflammatory and angiogenesis-related gene expression by real time PCR.
Results :
NLY01 significantly decreased both the avascular area and neovascular tuft area as compared with PBS injection. In the mouse retina, GLP-1R was mainly expressed by Iba1+ cells. After injection, NLY01-FITC co-localized with Iba1+ cells in the intermediate layer of retinas at P13. At P15 and P17, NLY01-FITC co-localized with Iba1+ cells in the superficial layer of avascular retina and in neovascular tufts. In BV-2 cells, NLY01 significantly suppressed the expression of inflammatory and angiogenesis-related genes induced by LPS.
Conclusions :
NLY01 significantly promoted re-vascularization and ameliorated retinal angiogenesis in the OIR model, and these effects could be mediated by suppressing the microglial inflammation. NLY01 may be a potential treatment for retinal angiogenesis. Further study is required to elucidate the molecular mechanisms involved.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.