With age many retinal neurons are lost. In humans the rod photoreceptor population in the perimacular region is subject to approximately 30% loss over life. Those that remain have been reported to suffer from extensive convolutions and localized swellings of their outer segments abnormally increasing their disc content and outer segment length. Here we examine quantitatively age-related changes in rat rod photoreceptors. The rat retina is ∼97% rod dominated. Here, aged rods showed significant reductions in outer segment length. The discs in their outer segments had a similar density, irrespective of whether they were young or old, however, in aged animals a higher proportion were misregistered. Surprisingly, in all of the tissue examined, we found no evidence for any convolution of outer segments or localized swelling as reported in humans, rather all remained straight. There are methodological differences between the research reported here and that undertaken on human retinae. There are also major differences in overall retinal architecture between humans and rodents that could contribute to differences in the aging process of individual cells. If it is the case that individual photoreceptors age differently in rodents compared to humans, it may pose significant problems for the use of this animal model in studies of ageing and age related outer retinal disease.

The present study has examined the spatial and temporal expression patterns of various proteins associated with the structure and function of mature photoreceptor outer segments in the developing ferret's retina using immunocytochemistry and RT-PCR. One set of proteins, including rod opsin, arrestin, and recoverin, was detected progressively in photoreceptors as they became postmitotic, being expressed well before the differentiation of outer segments. A second set of proteins, including β- and γ-transducin, cGMP-phosphodiesterase, phosducin, rhodopsin kinase, rod cGMP-gated cation channel protein, and peripherin, displayed a contrasting temporal onset and pattern of spatial emergence. These latter proteins first became detectable either shortly before or coincident with outer segment formation, and were expressed simultaneously in both older and younger photoreceptor cells. A third set, the short wavelength-sensitive (SWS) and medium wavelength-sensitive (MWS) cone opsin proteins, was the last to be detected, but materialized in a spatio-temporal pattern reminiscent of the neurogenetic gradient of the cones. These different spatial and temporal patterns indicate that cellular maturation must play a primary role in regulating the onset of expression of some of these proteins, while extrinsic signals must act to coordinate the expression of other proteins across photoreceptors of different ages.

In many vertebrate retinas the outer segments of rod photoreceptors have multiple incisures, that is, there are numerous indentations in the highly curved membrane forming the edge of their disks and in the plasma membrane enclosing the entire stack of disks. Immunofluorescent localization of tubulin in amphibian photoreceptors yielded a novel series of thin, parallel, fluorescent lines in rod outer segments that extended their full length and coincided with their multiple incisures. Electron-microscopic examination of amphibian retinas revealed the structures responsible for this fluorescence: longitudinally oriented microtubules were associated with incisures at heights throughout rod outer segments. These microtubules were located between the disk rims and the overlying plasma membrane, in the small cytoplasmic compartment at the mouth of incisures; the microtubules and membranes were separated from each other by distances that were uniform, as though interconnected by filaments described in other studies. Thus, in amphibian rod outer segments the incisures mark the site of a cytoskeletal system containing longitudinal microtubules distinct from those of the ciliary axoneme, linked by filaments to the adjacent membranes. This cytoskeleton is expected to be important for the normal structure, function, and renewal of rod outer segments. In amphibian cone outer segments, which do not have incisures, the only anti-tubulin immunofluorescence and the only microtubules were at the axoneme. These findings may help elucidate the diverse properties of rods and cones in many vertebrate retinas and could prove relevant for human retinal degenerations.