A detailed knowledge of the status of the retina in neurodegenerative conditions is a crucial point for the development of therapeutics in retinal pathologies and to translate eye research to CNS disease. In this context, manipulating signaling pathways that lead to neuronal regeneration offers an excellent opportunity to substitute damaged cells and, thus, restore the tissue functionality. Alternative systems and methods are increasingly being considered to replace/reduce in vivo approaches in the study of retina pathophysiology. Herein, we present recent data obtained from the zebrafish (Danio rerio) and the fruit fly Drosophila melanogaster that bring promising advantages into studying and modeling, at a preclinical level, neurodegeneration and regenerative approaches in retinal diseases. Indeed, the regenerative ability of vertebrate model zebrafish is particularly appealing. In addition, the fruit fly is ideal for regenerative studies due to its high degree of conservation with vertebrates and the broad spectrum of genetic variants achievable. Furthermore, a large part of the drosophila brain is dedicated to sight, thus offering the possibility of studying common mechanisms of the visual system and the brain at once. The knowledge acquired from these alternative models may help to investigate specific well-conserved factors of interest in human neuroregeneration after injuries or during pathologies.