Methods and compositions for treating retinal diseases comprising therapeutic amounts of a compound selected from a normal Puf-A gene product, an active polypeptide fragment thereof, an analog thereof or a peptidomimetic thereof. Vectors, including AAV vectors comprising the therapeutic compound are provided. Puf-A compositions suitable for subretinal, intravitreal, topical, subconjunctival, retrobulbar, periocular, suprachoroidal, or intraocular administration are provided. Methods for screening siRNA, RNAi and shRNA, small molecules and monoclonal antibodies that inhibit Puf-A target activity and reduce apoptosis are provided.