Abstract
Fibroblast growth factors (Fgf) are secreted signaling molecules that have mitogenic, patterning, neurotrophic and angiogenic properties. Their importance during embryonic development in patterning and morphogenesis of the vertebrate eye is well known, but less is known about the role of Fgfs in the adult vertebrate retina. To address Fgf function in adult retina, we determined the spatial distribution of components of the Fgf signaling pathway in the adult zebrafish retina. We detected differential expression of Fgf receptors, ligands and downstream Fgf targets within specific retinal layers. Furthermore, we blocked Fgf signaling in the retina, by expressing a dominant negative variant of Fgf receptor 1 conditionally in transgenic animals. After blocking Fgf signaling we observe a fast and progressive photoreceptor degeneration and disorganization of retinal tissue, coupled with cell death in the outer nuclear layer. Following the degeneration of photoreceptors, a profound regeneration response is triggered that starts with proliferation in the inner nuclear layer. Ultimately, rod and cone photoreceptors are regenerated completely. Our study reveals the requirement of Fgf signaling to maintain photoreceptors and for proliferation during regeneration in the adult zebrafish retina.
Highlights
Teleost fish possess a tremendous ability to regenerate injured organs [1,2,3,4,5,6,7,8]
Fibroblast growth factors (Fgf) pathway expression in the adult neural retina The role of Fgf signaling in the adult zebrafish retina is little studied, we initially investigated the expression profile of several Fgf receptors (Fgfr), ligands and target genes by in situ hybridization (Fig. 1 A–M)
Expression profiles of four of five Fgf receptors are detected in the adult zebrafish retina. fgfr1a and fgfr2 are expressed in the inner half of the inner nuclear layer (INL), whereas fgfr3 expression is complementary, in the outer half of the INL (Fig. 1A–C)
Summary
Teleost fish possess a tremendous ability to regenerate injured organs [1,2,3,4,5,6,7,8]. We use the zebrafish retina to study processes during adult retinal degeneration and regeneration. The adult zebrafish is able to restore the complex architecture and function of the neural retina following injury, and two different cell sources are involved in the process of retinal neurogenesis and regeneration. The loss of rods proceeds very slowly and complete loss is observed only after long-term suppression of Fgf signaling in mice that are several months old [25,26,27] These studies suggest that Fgf signaling plays a crucial role in tissue homeostasis. The aim of our study is to understand the role of Fgf signaling in homeostasis and after injury in the adult zebrafish retina. Taken together our results suggest that Fgf signaling is required for maintenance of photoreceptor cells in the adult retina and plays a role in proliferation during photoreceptor regeneration
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