Time-resolved expression analysis comparing two selective retinal cell ablation paradigms in zebrafish reveals shared and cell-specific regenerative regulatory networks

Abstract

AbstractZebrafish are an effective model organism for retinal regeneration studies. Regenerated retinal cells are derived from Müller glia (MG) stem cells. Mammalian MG can also produce new retinal neurons; however, this regenerative potential remains dormant in the absence of genetic and/or chemical stimulation. An understanding of how the regenerative potential of MG is regulated could aid efforts to promote regeneration therapeutically. Following widespread retinal cell death, developmental signaling coordinates regeneration. Less is known about how MG respond to the loss of specific cell types, i.e., paradigms similar to retinal degenerative diseases. To address this, transcriptomic responses to the selective loss of rod photoreceptors or retinal bipolar cells were compared over twelve timepoints spanning cell degeneration and regeneration. Shared and paradigm-specific expression changes were identified throughout regeneration. Overall, paradigm-specific changes predominated, suggesting cell-specific mechanisms for activating MG stem cells. One particularly interested finding new for retinal regeneration was early regulation of SOCS family genes. These are associated with stat3 activation and the JAK/STAT pathway which has been well documented in similar studies and was further supported in our analyses. These data support the concept that selective retinal cell loss can elicit cell-specific regenerative programs and provide novel insights into retinal regeneration.