In the present study, we tested this hypothesis in two commonly used RGC injury models induced by retinal ischemia/reperfusion (I/R) or ocular hypertension and explored the potential mechanism of p58IPK neuroprotection and its interaction with mesencephalic astrocyte-derived neurotrophic factor (MANF), an ER stress responsive neurotrophic factor. This evidence concerns the gene MANF and ocular hypertension.