Retinal regeneration in adult zebrafish

Unlike mammals, teleost fish have the ability to regenerate their retina after damage. Recent studies have shown that the eyes of other vertebrates, including humans, contain retinal stem cells which might one day be manipulated in order to promote retinal regeneration (Ahmad et al., 2000 Tropepe et al., 2000 Karl et al., 2008). Despite numerous studies, an existing knowledge gap continues to make this manipulation an impossibility. In order to contribute to our further understanding of the regenerating process, I address the following questions in this dissertation: 1. How successful is retinal regeneration at recovering vision following damage? 2. Are there conditions that optimize regeneration? 3. Can vision be restored even if underlying pathology is present? The main goal of this study is to characterize regeneration in adult zebrafish and identify conditions and/or factors that impact the regenerative process. This goal was achieved by studying comparative regeneration process in selective vs. broad retinal damage in adult zebrafish and by characterizing the eye of a high intraocular pressure (IOP) zebrafish mutant, bugeye .Comparative studies of broad vs. selective retinal damage models showed that functional and histological regeneration occurs faster with fewer histological errors in selective damage as compared to broad damage, suggesting that regenerative therapies may work better on damaged retinas that contain healthy cells. Investigation of the bugeye eye phenotype showed that the bugeye are incapable of maintaining visual function despite ongoing proliferation and lack of detectable cell death. These data show that regenerative capacity may not confer resistance to pathology, suggesting that successfully treating pathology should be the first step in any regenerative medical intervention. Understanding regeneration in adult zebrafish is very important in order to gain insight into the failed regeneration response in mammals, and to optimize the outcome of any therapeutic regeneration strategies.