Inhibition of Renin-Angiotensin System Prevents Neurodegeneration in a Mouse Model of Normal Tension Glaucoma.

Glaucoma is the leading cause of blindness in Japan, and an alternative treatment to lowering intraocular pressure (IOP) is required to manage this disease. We found that expressions of angiotensin II type 1 receptor (AT1-R) and Toll-like receptor 4 (TLR4) were increased in retinal ganglion cells (RGCs) and retinal Müller glia in normal tension glaucoma (NTG) model mouse. The orally active AT1-R antagonist candesartan suppressed TLR4 and lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expressions, especially in retinal Müller glia. Treatment with candesartan was effective for RGC protection without affecting IOP. These results suggest that the renin-angiotensin system is involved in the innate immune responses in both neural and glial cells, and AT1-R antagonist may exert IOP-independent neuroprotective effects.