Our study shows that MTS AAV transfer of wild-type human ND4 is nonpathogenic to host mitochondria, and supports our previous studies that indicate an MTS AAV-ND4 can be used to rescue visual loss and optic neuropathy induced by the mutant ND4 allele responsible for most cases of LHON [14]. Here, MT-ND4 is linked to Optic neuropathy.