Abstract
Purpose :
To investigate the role of irbesartan, an angiotensin II receptor type I blocker in the retinal ganglion cell (RGC) survival in an ex vivo mouse organotypic retinal explant model and in in vivo optic nerve crush glaucoma model.
Methods :
For the ex vivo model, eyes from C57BL/6 mice were enucleated immediately post mortem to make two retinal explants per eye. Explants were culutred at an air/medium interface on membrane inserts for 4 days and treated either with the AT1R receptor antagonist irbesartan (10uM) or agiotensin II, an AT1R agonist (2uM) against controls. For the in vivo optic nerve crush model: anesthetized mice had a self clamping forceps placed around the optic nerve behind the globe for 10 seconds. Animals were subsequently treated with either irbesartan eye drops (10 uM twice daily) for 7 days or vehicle prior to euthenasia and enucleation for analysis. Viable RGC density in both models was analyzed by RNA-binding protein with multiple splicing (RBPMS) immunohistochemistry.
Results :
Retinal explants treated with irbesartan demonstrated a 4-fold (p = 0.002) increase in number of surviving RGCs on day 4 compared to the control. There was no RBPMS staining of RGCs in angiotensin II treated explants on day 4 of the treatment. Cell viability was positively correlated with a reduction in intracellular superoxide formation in the treated explants. In in vivo model, the number of surviving RGCs was significantly higher (p < 0.05) in Irbesartan treated animals when compared to RGCs treated with vehicle only.
Conclusions :
Irbesartan increased RGC survival in both ex vivo and in vivo glaucoma models suggesting an important role in neuroprotection in eye diseases such as glaucoma with the possibility of localised therapy.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.