Will I see you again? The promise, power, and problems of retinal regeneration in fish

The vertebrate neural retina, the image forming component of the eye, offers a useful, clinically-relevant system for understanding nervous system development and regeneration. Within vertebrates, the teleost fish retina specifically has been the subject of intense study for its regenerative response to neuronal damage - a response that does not take place in mammals. While the field has recently focused upon molecular and cellular processes that initiate this response and generate new neurons, it is also important to evaluate the ultimate "success" of this process. True neural regeneration requires that the cells and tissues that replace those lost to damage, also restore their original structure and function. From this outcomes-based perspective, does retinal regeneration recapitulate the results of development? This paper reviews ∼50 years of effort and knowledge regarding the regeneration of retinal neuronal types and patterns, wiring of regenerated neurons within the retina and beyond, and physiological and behavioral studies of function of regenerated retina. Emphasis is placed upon goldfish and zebrafish model systems, as these have been popular, productive models for revealing both the process and the outcome of retinal regeneration. The outcome, as accumulated data suggest, is considered remarkable in the sense that several features of structure and function are restored. Regenerated retinas are structurally similar in comparison with undamaged retinas that developed and grew normally, with notable local patterning errors. A body of evidence suggests that these structural errors are not of great consequence for the re-establishment of retinal function that is centrally integrated to support simple, visually-mediated behaviors. However, functional tests have been limited in scope and scale, lacking rigorous applications of more sophisticated approaches to evaluate visual system circuitry. Such approaches are becoming possible in the zebrafish model. Fish models are upheld as outstanding resources for providing current and future knowledge of regeneration that can be translated to treat human retinal disorders.