Angiotensin-(1-7) Provides Potent Long-Term Neurorepair/Neuroregeneration in a Rodent White Matter Stroke Model: Nonarteritic Ischemic Optic Neuropathy (rNAION)

Nonarteritic anterior ischemic optic neuropathy (NAION) is an ischemic lesion of the anterior optic nerve (ON), currently untreatable due to the length of time from symptom onset until treatment. We evaluated angiotensin-(1-7) (Ang-(1-7)): the MAS1-receptor ligand, as a possible NAION treatment using the rodent NAION model (rNAION). Long-Evans rats were unilaterally rNAION-induced. One-day post-induction, lesion severity was quantified via optic nerve head (ONH) edema using spectral domain optical coherence tomography. Animals meeting rNAION induction criteria were randomized into (1) Subcutaneous Ang-(1-7) infusion for 28 days and (2) Vehicle. Visual function was assessed using both visual acuity and flash visual evoked potentials (fVEP). Tissues were collected >30d and RGC neurons were quantified by stereology. ONs were histologically examined for inflammation. Ang-(1-7) improved post-rNAION visual function. Ang-(1-7)-treated animals showed improved visual acuity (ANCOVA: <i>p</i> = 0.0084) and improved fVEP amplitudes (ANCOVA: <i>p</i> = 0.0378) vs vehicle controls. The relative degree of improvement correlated with ONH edema severity. Treated animals showed trends towards increased RGC survival, and reduced optic nerve inflammatory cell infiltration. Ang-(1-7) is the first agent effective ≥1 day after rNAION induction. Ang-(1-7) type agonists may be useful in improving long-term function and neuronal survival in clinical NAION and other forms of white matter ischemia.