Disclosed are isolated mutant erythropoietin (EPO) polypeptides, functional fragment thereof, nucleic acid encoding such peptides, vectors including such nucleic acids and compositions including such peptides and nucleic acids. The mutant EPO peptides are unique in that they include a substitution at amino acid position number 76, such as a glutamic acid for arginine substitution at position 76. This substitution inhibits erythropoietic activity while retaining their neuroprotection. Also disclosed are methods of treating or inhibiting neuronal degeneration, reducing or inhibiting one or more symptoms associated with neuronal degeneration and/or glaucoma in a subject. The methods include administering a therapeutically effective amount of a isolated mutant erythropoietin EPO polypeptide, an expression vector encoding such a mutant erythropoietin EPO polypeptide, a viral particle including an expression vector, or a composition, thereby treating or inhibiting neuronal degeneration in the subject.