Structure of the retina. A: Microphotograph of a cross-section through the retina of an adult zebrafish, showing the different cellular and synaptic retinal layers. B: Diagram of the neural circuit of the retina, showing the six neuronal cell types and the two supporting cell types (Müller glia and retinal pigmented epithelium). In A, the scale bar = 25μm.

Expression of mdka and mdkb during retinal development. mdka (pink) is expressed in proliferating retinal progenitors, whereas mdkb (green) is expressed in newly post-mitotic cells. Between 72 and 120 hpf, mdka is transiently expressed in Müller glia.

Expression of mdka and mdkb in the adult zebrafish retina. A: In situ hybridization showing the expression of mdka in horizontal cells (arrows). B: In situ hybridization showing the expression of mdkb in amacrine cells (arrowhead) in the inner tier of the inner nuclear layer and ganglion cells (arrow). GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer. Scale bar = 25μm.

Circadian regulation of Mdka levels in the adult zebrafish retina. The expression of Mdka increases in anticipation of light onset and decreases throughout the daylight hours, reaching a minimum during the night.

Midkine expression in zebrafish retinal regeneration. A: Cone photoreceptors are immunolabelled (red signal) in an unlesioned retina. B: Photoreceptors are nearly completely killed following exposure to a photolytic lesion. C: In situ hybridization showing that mdka is expressed in proliferating photoreceptor progenitors (pink label) following photoreceptor death. The mdka message co-localizes with antibody staining for bromodeoxyuridine (BrdU, green signal). D: Fourteen days following the onset of a photolytic lesion, rod (not shown) and cone photoreceptors (red signal) are regenerated. E: Timeline of the different processes that occur in the adult zebrafish retina after light-induced damage and the proliferative response of Müller glia. The pink colour represents the onset and duration of mdka expression in Müller glia and photoreceptor progenitors. Scale bar = 25 μm (C) and 50μm (A, B and D). GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer; dpl: days post-lesion.