Ultrastructure of photoreceptors in Rp1-mycmice. Eyes of mice with indicated ages and genotypes were embedded in Epon, sectioned at 60- to 80-nm thickness and evaluated by electron microscopy. (A)Outer segments in the P14 wild-type retina appeared as straight, parallel cylinders from inner segments to the RPE. The stacks of discs were organized and perpendicular to the long axis of the cell (left). In contrast, outer segments in P14 Rp1myc/mycmice were disorganized. Small packets of discs were scattered in the space between the inner segments and RPE (middle). Close examination of the disorganized discs (right)showed that these small packets contained approximately 20 to 40 discs with diameters two to three times normal (2–4 μm), oriented obliquely or parallel to the long axis of the cell. Although abnormally oriented, the discs in Rp1myc/mycretinas were intact, with identifiable rims. (B)The morphology of the photoreceptor axoneme and newly forming discs at the base of the outer segments were examined at P10. The nascent discs were tightly aligned along the axoneme (arrowhead)at the base of the outer segment in the wild-type mice (left). In the Rp1myc/mycmice, even the early lip (L) of new membrane evagination at the base of the outer segment was misoriented, and nascent discs were parallel to the axoneme (arrowhead, middle). In addition, the disc rims were no longer associated with the axoneme. A cross section showed a normal axoneme structure, but also demonstrated discs oriented parallel to the axis of the outer segment (right). (C)At age P30 the outer segment dysplasia was more severe, with shortening and disorganization of outer segments structures in the photoreceptors of Rp1myc/mycmice (middle), compared with the wild-type control (left). Misoriented disc stacks (arrowhead)and short packets of discs (*)were still observed (right). (D)The ultrastructure of photoreceptors in 8-month-old Rp1+/mycmice (right)was grossly normal compared with that of wild-type mice (left). CC, connecting cilium; IS, inner segment; OS, outer segment.