Defective intraretinal vascular development in <i>Foxn4</i>^-/- mice.

<p>(<b>A-I</b>) Vascular development relative to Müller cell nuclei (Sox9), rod bipolar cells (PKCalpha), and photoreceptors (Recoverin) at the indicated time points. <i>Foxn4</i>^-/- retinas display no intraretinal capillaries at P10, only sporadic isolectinB4 positive macrophages are seen within the retina. By P14, the NFL, IPL, and OPL are vascularized in WT mice, while <i>Foxn4</i>^-/- mice exhibit only a single, aberrant intraretinal vascular plexus. Capillaries in this plexus are found in a range of locations, i.e., overlapping with Sox9 positive nuclei (white arrow in G), below rod bipolar cells, and in varying distances from the recoverin positive photoreceptors. Between P10 and P14 the <i>Foxn4</i>^-/- retina looses lamination in the OPL region, and by P21 frequent splits in the INL portion of the retina are observed (H, right panel). Rod bipolar cell neurites sprout into the ONL. (<b>J-O</b>) Confocal z-projections of the indicated vascular layers. Panels were generated by stitching 5 projections per panel. Vascular development in the NFL is delayed at P10 in <i>Foxn4</i>^-/- mice but less affected by P14. No intraretinal capillaries are present in P10 <i>Foxn4</i>^-/- mice, but many isolectinB4 positive macrophages are present (inset in K shows enlarged macrophage). The ectopic intraretinal plexus is poorly developed by P14. GCL, ganglion cell layer; ONL, outer nuclear layer; IPL, inner plexiform layer; OPL, outer plexiform layer; NFL, nerve fiber layer. Scale bars: 20 μm (sections), 50 μm (whole mounts).