Figure 1. Retinal degeneration and vision loss in the Cln6^nclf mouse.

Cell loss and structural degenerative changes occur in the retina of Cln6^nclf mice. (A) Comparison of gross morphological changes over time in retina of Cln6^nclf mice and their respective age-matched WT controls was done to determine mechanism of degeneration. (B) Micrographs (4X) show a section of one retinal hemisphere. (C) At P0 all layers are present and of equal thickness. By 3 months of age the Cln6^nclf retina has begun to narrow and shows a distinct loss of the rods and cones while the overall cytoarchitecture remains intact. By 9 months the rods and cones are nearly absent and the outer plexiform layer is virtually nonexistent with the merging of a much thinned outer and inner nuclear layers. Additionally, there is a distinct narrowing of the inner plexiform layer. [RC-Rode/Cone layer; ONL-Outer nuclear layer; OPL-Outer plexiform later; INL-Inner nuclear layer; IPL-Inner plexiform layer; GCL-Ganglion cell layer]. (D) At 8 months of age, Cln6^nclf mice displayed a significant reduction in visual acuity in a visual cliff assay. Mutant mice were unable to distinguish between a “safe” region of the visual cliff box versus the “unsafe” cliffed portion, spending equal time between the two regions. [Mean (in seconds) +/- SEM, n = 6–9 mice per group (**p≤0.01)].