The ageing photoreceptor

2007 ◽  
Vol 24 (2) ◽  
pp. 151-155 ◽  
Author(s):  
ALEXANDER CUNEA ◽  
GLEN JEFFERY
Keyword(s):  
Aging Process ◽  
Outer Segment ◽  
Retinal Disease ◽  
Segment Length ◽  
Rod Photoreceptor ◽  
Retinal Neurons ◽  
Rod Photoreceptors ◽  
Outer Segments ◽  
Age Related ◽  
Similar Density

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.

scholarly journals Macular Pigment Optical Density and Photoreceptor Outer Segment Length as Predisease Biomarkers for Age-Related Macular Degeneration

2020 ◽  
Vol 9 (5) ◽  
pp. 1347 ◽  
Author(s):  
Norihiro Nagai ◽  
Sakiko Minami ◽  
Misa Suzuki ◽  
Hajime Shinoda ◽  
Toshihide Kurihara ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Optical Density ◽  
Outer Segment ◽  
Macular Pigment ◽  
Age Related Macular Degeneration ◽  
Segment Length ◽  
Macular Pigment Optical Density ◽  
Photoreceptor Outer Segment ◽  
Age Related ◽  
Fellow Eyes

To explore predisease biomarkers, which may help screen for the risk of age-related macular degeneration (AMD) at very early stages, macular pigment optical density (MPOD) and photoreceptor outer segment (PROS) length were analyzed. Thirty late AMD fellow eyes, which are at high risk and represent the predisease condition of AMD, were evaluated and compared with 30 age-matched control eyes without retinal diseases; there was no early AMD involvement in the AMD fellow eyes. MPOD was measured using MPS2® (M.E. Technica Co. Ltd., Tokyo, Japan), and PROS length was measured based on optical coherence tomography images. MPOD levels and PROS length in the AMD fellow eyes were significantly lower and shorter, respectively, than in control eyes. MPOD and PROS length were positively correlated in control eyes (R = 0.386; p = 0.035) but not in AMD fellow eyes. Twenty (67%) AMD fellow eyes met the criteria of MPOD < 0.65 and/or PROS length < 35 μm, while only five (17%) control eyes did. After adjusting for age and sex, AMD fellow eyes more frequently satisfied the definition (p < 0.001; 95% confidence interval, 3.50–60.4; odds ratio, 14.6). The combination of MPOD and PROS length may be a useful biomarker for screening predisease AMD patients, although further studies are required in this regard.

scholarly journals Immunocytochemical localization of opsin in the cell membrane of developing rat retinal photoreceptors.

1984 ◽  
Vol 98 (5) ◽  
pp. 1788-1795 ◽  
Author(s):  
I Nir ◽  
D Cohen ◽  
D S Papermaster
Keyword(s):  
Plasma Membrane ◽  
Outer Segment ◽  
Plasma Membranes ◽  
Photoreceptor Cells ◽  
Rod Photoreceptor ◽  
Rod Photoreceptors ◽  
Retinal Photoreceptors ◽  
Retinal Rod ◽  
Ros Formation ◽  
Developing Rat

Mature retinal rod photoreceptors sequester opsin in the disk and plasma membranes of the rod outer segment (ROS). Opsin is synthesized in the inner segment and is transferred to the outer segment along the connecting cilium that joins the two compartments. We have investigated early stages of retinal development during which the polarized distribution of opsin is established in the rod photoreceptor cell. Retinas were isolated from newborn rats, 3-21 d old, and incubated with affinity purified biotinyl-sheep anti-bovine opsin followed by avidin-ferritin. At early postnatal ages prior to the development of the ROS, opsin is labeled by antiopsin on the inner segment plasma membrane. At the fifth postnatal day, as ROS formation begins opsin was detected on the connecting cilium plasma membrane. However, the labeling density of the ciliary plasma membrane was not uniform: the proximal cilium was relatively unlabeled in comparison with the distal cilium and the ROS plasma membrane. In nearly mature rat retinas, opsin was no longer detected on the inner segment plasma membrane. A similar polarized distribution of opsin was also observed in adult human rod photoreceptor cells labeled with the same antibodies. These results suggest that some component(s) of the connecting cilium and its plasma membrane may participate in establishing and maintaining the polarized distribution of opsin.

scholarly journals Light-Evoked Responses of the Retinal Pigment Epithelium: Changes Accompanying Photoreceptor Loss in the Mouse

2010 ◽  
Vol 104 (1) ◽  
pp. 391-402 ◽  
Author(s):  
Ivy S. Samuels ◽  
Gwen M. Sturgill ◽  
Gregory H. Grossman ◽  
Mary E. Rayborn ◽  
Joe G. Hollyfield ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Structural Changes ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Disease ◽  
Rod Photoreceptor ◽  
Evoked Responses ◽  
Photoreceptor Degeneration ◽  
Rod Photoreceptors ◽  
Slow Piii

Mutations in genes expressed in the retinal pigment epithelium (RPE) underlie a number of human inherited retinal disorders that manifest with photoreceptor degeneration. Because light-evoked responses of the RPE are generated secondary to rod photoreceptor activity, RPE response reductions observed in human patients or animal models may simply reflect decreased photoreceptor input. The purpose of this study was to define how the electrophysiological characteristics of the RPE change when the complement of rod photoreceptors is decreased. To measure RPE function, we used an electroretinogram (dc-ERG)-based technique. We studied a slowly progressive mouse model of photoreceptor degeneration ( Prph Rd2/+), which was crossed onto a Nyxnob background to eliminate the b-wave and most other postreceptoral ERG components. On this background, Prph Rd2/+ mice display characteristic reductions in a-wave amplitude, which parallel those in slow PIII amplitude and the loss of rod photoreceptors. At 2 and 4 mo of age, the amplitude of each dc-ERG component (c-wave, fast oscillation, light peak, and off response) was larger in Prph Rd2/+ mice than predicted by rod photoreceptor activity (RmP3) or anatomical analysis. At 4 mo of age, the RPE in Prph Rd2/+ mice showed several structural abnormalities including vacuoles and swollen, hypertrophic cells. These data demonstrate that insights into RPE function can be gained despite a loss of photoreceptors and structural changes in RPE cells and, moreover, that RPE function can be evaluated in a broader range of mouse models of human retinal disease.

scholarly journals Localization of peripherin/rds in the disk membranes of cone and rod photoreceptors: relationship to disk membrane morphogenesis and retinal degeneration.

1992 ◽  
Vol 116 (3) ◽  
pp. 659-667 ◽  
Author(s):  
K Arikawa ◽  
L L Molday ◽  
R S Molday ◽  
D S Williams
Keyword(s):  
Plasma Membrane ◽  
Retinal Degeneration ◽  
Outer Segment ◽  
Photoreceptor Cells ◽  
Growth Stages ◽  
Rod Outer Segments ◽  
Rod Photoreceptor ◽  
Outer Segments ◽  
Disk Membrane ◽  
Membrane Morphogenesis

The outer segments of vertebrate rod photoreceptor cells consist of an ordered stack of membrane disks, which, except for a few nascent disks at the base of the outer segment, is surrounded by a separate plasma membrane. Previous studies indicate that the protein, peripherin or peripherin/rds, is localized along the rim of mature disks of rod outer segments. A mutation in the gene for this protein has been reported to be responsible for retinal degeneration in the rds mouse. In the present study, we have shown by immunogold labeling of rat and ground squirrel retinas that peripherin/rds is present in the disk rims of cone outer segments as well as rod outer segments. Additionally, in the basal regions of rod and cone outer segments, where disk morphogenesis occurs, we have found that the distribution of peripherin/rds is restricted to a region that is adjacent to the cilium. Extension of its distribution from the cilium coincides with the formation of the disk rim. These results support the model of disk membrane morphogenesis that predicts rim formation to be a second stage of growth, after the first stage in which the ciliary plasma membrane evaginates to form open nascent disks. The results also indicate how the proteins of the outer segment plasma membrane and the disk membranes are sorted into their separate domains: different sets of proteins may be incorporated into membrane outgrowths during different growth stages of disk morphogenesis. Finally, the presence of peripherin/rds protein in both cone and rod outer segment disks, together with the phenotype of the rds mouse, which is characterized by the failure of both rod and cone outer segment formation, suggest that the same rds gene is expressed in both types of photoreceptor cells.

Movement of retinal along cone and rod photoreceptors

1994 ◽  
Vol 11 (2) ◽  
pp. 389-399 ◽  
Author(s):  
Jing Jin ◽  
Gregor J. Jones ◽  
M. Carter Cornwall
Keyword(s):  
Cell Body ◽  
Dark Adaptation ◽  
Visual Pigment ◽  
Outer Segment ◽  
Light Adaptation ◽  
Rod Photoreceptors ◽  
Rod Outer Segment ◽  
Rods And Cones ◽  
Outer Segments ◽  
Rod Cell

AbstractSingle isolated photoreceptors can be taken through a visual cycle of light adaptation by bleaching visual pigment, followed by dark adaptation when supplied with 11–cis retinal. Light adaptation after bleaching is manifested by faster response kinetics and a permanent reduction in sensitivity to light flashes, presumed to be due to the presence of bleached visual pigment. The recovery of flash sensitivity during dark adaptation is assumed to be due to regeneration of visual pigment to pre-bleach levels. In previous work, the outer segments of bleached, light-adapted cells were exposed to 11–cis retinal. In the present work, the cell bodies of bleached photoreceptors were exposed. We report a marked difference between rods and cones. Bleached cones recover sensitivity when their cell bodies are exposed to 11–cis retinal. Bleached rods do not. These results imply that retinal can move freely along the cone photoreceptor, but retinal either is not taken up by the rod cell body or retinal cannot move from the rod cell body to the rod outer segment. The free transfer of retinal along cone but not along rod photoreceptors could explain why, during dark adaptation in the retina, cones have access to a store of 11–cis retinal which is not available to rods. Additional experiments investigated the movement of retinal along bleached rod outer segments. The results indicate that retinal can move along the rod outer segment, but that this movement is slow, occurring at about the same rate as the regeneration of visual pigment.

scholarly journals A Zebrafish Model of Retinitis Pigmentosa Shows Continuous Degeneration and Regeneration of Rod Photoreceptors

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2242
Author(s):  
Abirami Santhanam ◽  
Eyad Shihabeddin ◽  
Joshua A. Atkinson ◽  
Duc Nguyen ◽  
Ya-Ping Lin ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Transgenic Fish ◽  
Model Systems ◽  
Brdu Incorporation ◽  
Rod Photoreceptor ◽  
Adult Fish ◽  
Zebrafish Model ◽  
Rod Photoreceptors ◽  
Outer Segments ◽  
Regenerative Therapies

More than 1.5 million people suffer from Retinitis Pigmentosa, with many experiencing partial to complete vision loss. Regenerative therapies offer some hope, but their development is challenged by the limited regenerative capacity of mammalian model systems. As a step toward investigating regenerative therapies, we developed a zebrafish model of Retinitis Pigmentosa that displays ongoing regeneration. We used Tol2 transgenesis to express mouse rhodopsin carrying the P23H mutation and an epitope tag in zebrafish rod photoreceptors. Adult and juvenile fish were examined by immunofluorescence, TUNEL and BrdU incorporation assays. P23H transgenic fish expressed the transgene in rods from 3 days post fertilization onward. Rods expressing the mutant rhodopsin formed very small or no outer segments and the mutant protein was delocalized over the entire cell. Adult fish displayed thinning of the outer nuclear layer (ONL) and loss of rod outer segments, but retained a single, sparse row of rods. Adult fish displayed ongoing apoptotic cell death in the ONL and an abundance of proliferating cells, predominantly in the ONL. There was a modest remodeling of bipolar and Müller glial cells. This transgenic fish will provide a useful model system to study rod photoreceptor regeneration and integration.

scholarly journals Loss of Pde6a Induces Rod Outer Segment Shrinkage and Visual Alterations in pde6aQ70X Mutant Zebrafish, a Relevant Model of Retinal Dystrophy

2021 ◽  
Vol 9 ◽  
Author(s):  
Lucie Crouzier ◽  
Camille Diez ◽  
Elodie M. Richard ◽  
Nicolas Cubedo ◽  
Clément Barbereau ◽  
...  
Keyword(s):  
Visual Function ◽  
Outer Segment ◽  
Retinal Dystrophy ◽  
Segment Length ◽  
Rod Photoreceptor ◽  
The Novel ◽  
Loss Of Function ◽  
Rod Outer Segment ◽  
Inherited Retinal Degeneration ◽  
Photoreceptor Death

Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degeneration with 1/4,000 people being affected. The vision alteration primarily begins with rod photoreceptor degeneration, then the degenerative process continues with cone photoreceptor death. Variants in 71 genes have been linked to RP. One of these genes, PDE6a is responsible for RP43. To date no treatment is available and patients suffer from pronounced visual impairment in early childhood. We used the novel zebrafish pde6aQ70X mutant, generated by N-ethyl-N-nitrosourea at the European Zebrafish Resource Centre, to better understand how PDE6a loss of function leads to photoreceptor alteration. Interestingly, zebrafish pde6aQ70X mutants exhibited impaired visual function at 5 dpf as evidenced by the decrease in their visual motor response (VMR) compared to pde6aWT larvae. This impaired visual function progressed with time and was more severe at 21 dpf. These modifications were associated with an alteration of rod outer segment length at 5 and 21 dpf. In summary, these findings suggest that rod outer segment shrinkage due to Pde6a deficiency begins very early in zebrafish, progresses with time. The zebrafish pde6aQ70X mutant represents an ideal model of RP to screen relevant active small molecules that will block the progression of the disease.

Localization of kinesin superfamily proteins to the connecting cilium of fish photoreceptors

1996 ◽  
Vol 109 (4) ◽  
pp. 889-897 ◽  
Author(s):  
P.L. Beech ◽  
K. Pagh-Roehl ◽  
Y. Noda ◽  
N. Hirokawa ◽  
B. Burnside ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Basal Body ◽  
Outer Segment ◽  
Rod Photoreceptors ◽  
Outer Segments ◽  
Immunological Tests ◽  
Peptide Antibody ◽  
N Terminus ◽  
Kinesin Superfamily ◽  
Rod Cell

Kinesin superfamily proteins (KIFs) are probable motors in vesicular and non-vesicular transport along microtubular tracks. Since a variety of KIFs have been recently identified in the motile flagella of Chlamydomonas, we sought to ascertain whether KIFs are also associated with the connecting cilia of vertebrate rod photoreceptors. As the only structural link between the rod inner segment and the photosensitive rod outer segment, the connecting cilium is thought to be the channel through which all material passes into and out of the outer segment from the rod cell body. We have performed immunological tests on isolated sunfish rod inner-outer segments (RIS-ROS) using two antibodies that recognize the conserved motor domain of numerous KIFs (anti-LAGSE, a peptide antibody, and anti-Klp1 head, generated against the N terminus of Chlamydomonas Klp1) as well as an antibody specific to a neuronal KIF, KIF3A. On immunoblots of RIS-ROS, LAGSE antibody detected a prominent band at approximately 117 kDa, which is likely to be kinesin heavy chain, and Klp1 head antibody detected a single band at approximately 170 kDa; KIF3A antibody detected a polypeptide at approximately 85 kDa which co-migrated with mammalian KIF3A and displayed ATP-dependent release from rod cytoskeletons. Immunofluorescence localizations with anti-LAGSE and anti-Klp1 head antibodies detected epitopes in the axoneme and ellipsoid, and immunoelectron microscopy with the LAGSE antibody showed that the connecting cilium region was particularly antigenic. Immunofluorescence with anti-KIF3A showed prominent labelling of the connecting cilium and the area surrounding its basal body; the outer segment axoneme and parts of the inner segment coincident with microtubules were also labelled. We propose that these putative kinesin superfamily proteins may be involved in the translocation of material between the rod inner and outer segments.

scholarly journals The Relationship Between Perifoveal L-Cone Isolating Visual Acuity and Cone Photoreceptor Spacing—Understanding the Transition Between Healthy Aging and Early AMD

2021 ◽  
Vol 13 ◽  
Author(s):  
Rigmor C. Baraas ◽  
Åshild Horjen ◽  
Stuart J. Gilson ◽  
Hilde R. Pedersen
Keyword(s):  
Outer Segment ◽  
Healthy Aging ◽  
Segment Length ◽  
Retinal Eccentricity ◽  
Cone Photoreceptor ◽  
Cone Structure ◽  
Age Related ◽  
Risk Of Progression ◽  
The Relationship ◽  
Cone Density

Background: Age-related macular degeneration (AMD) is a multifactorial degenerative disorder that can lead to irreversible loss of visual function, with aging being the prime risk factor. However, knowledge about the transition between healthy aging and early AMD is limited. We aimed to examine the relationship between psychophysical measures of perifoveal L-cone acuity and cone photoreceptor structure in healthy aging and early AMD.Methods and Results: Thirty-nine healthy participants, 10 with early AMD and 29 healthy controls were included in the study. Multimodal high-resolution retinal images were obtained with adaptive-optics scanning-light ophthalmoscopy (AOSLO), optical-coherence tomography (OCT), and color fundus photographs. At 5 degrees retinal eccentricity, perifoveal L-cone isolating letter acuity was measured with psychophysics, cone inner segment and outer segment lengths were measured using OCT, while cone density, spacing, and mosaic regularity were measured using AOSLO. The Nyquist sampling limit of cone mosaic (Nc) was calculated for each participant. Both L-cone acuity and photoreceptor inner segment length declined with age, but there was no association between cone density nor outer segment length and age. A multiple regression showed that 56% of the variation in log L-cone acuity was accounted for by Nc when age was taken into account. Six AMD participants with low risk of progression were well within confidence limits, while two with medium-to-severe risk of progression were outliers. The observable difference in cone structure between healthy aging and early AMD was a significant shortening of cone outer segments.Conclusion: The results underscore the resilience of cone structure with age, with perifoveal functional changes preceding detectable changes in the cone photoreceptor mosaic. L-cone acuity is a sensitive measure for assessing age-related decline in this region. The transition between healthy aging of cone structures and changes in cone structures secondary to early AMD relates to outer segment shortening.

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