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Effect of photoreceptor degeneration on circadian photoreception and free-running period in the Royal College of Surgeons rat.

ABSTRACT: The study of how the retina processes the photic information required for the entrainment of the circadian system is an exciting new topic in retinal neurobiology. We have recently shown that in RCS/N-rdy rats melanopsin mRNA levels are dramatically reduced (about 90%) and melanopsin immunoreactivity cannot be detected in the retina of these rats at 60 days of age. Although RCS/N-rdy rats are a widely used model to investigate mechanisms of photoreceptor degeneration, no study has investigated circadian photoreception in these animals. The aim of this study was to examine circadian photoreception in RCS/N-rdy(+) (rdy(+)) rats homozygous for the normal rdy allele and age-matched RCS/N-rdy (rdy) homozygotes with retinal dystrophy. No differences between RCS/N-rdy and rdy(+) were observed in light-induced phase shift of locomotor activity at the three light intensities used (1 x 10(-3), 1 x 10(-1), and 1 x 10(1) microW cm(-2)). Surprisingly, we observed that in RCS/N-rdy the free-running period of the circadian rhythm of locomotor activity was shorter (P<0.01) than in rdy(+), thus suggesting that photoreceptor degeneration may affect the free-running period of the locomotor activity rhythm.

SUBMITTER: Tosini G

PROVIDER: S-EPMC1939936 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Effect of photoreceptor degeneration on circadian photoreception and free-running period in the Royal College of Surgeons rat.

Tosini Gianluca G Aguzzi Jacopo J Bullock Nicole M NM Liu Cuimei C Kasamatsu Manami M

Brain research 20070301

The study of how the retina processes the photic information required for the entrainment of the circadian system is an exciting new topic in retinal neurobiology. We have recently shown that in RCS/N-rdy rats melanopsin mRNA levels are dramatically reduced (about 90%) and melanopsin immunoreactivity cannot be detected in the retina of these rats at 60 days of age. Although RCS/N-rdy rats are a widely used model to investigate mechanisms of photoreceptor degeneration, no study has investigated c ...[more]

PMID: 17382912

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Project description:Prior structural studies of posterior subcapsular cataract (PSC) development in Royal College of Surgeons (RCS) rats suggest that migration of basal fiber ends was disrupted, ultimately resulting in a PSC. Therefore the goal of this study was to assess the overall migration patterns as well as changes to the structure and cytoskeleton of basal fiber ends during PSC development.Lenses from 48 RCS dystrophic rats (RCS/Lav) and 24 genetically matched control animals (RCS-rdy(+)/Lav) from 2 to 8 weeks old were examined. Equatorial diameters were measured and suture patterns were photographed immediately following enucleation/dissection. Right eye lenses were fixed and processed to visualize the actin cytoskeleton via laser scanning confocal microscopy (LSCM), left eye lenses were decapsulated, fixed and processed for scanning electron microscopy (SEM). Scaled 3D-computer assisted drawings (CADs) and animations were constructed from the data to depict the changes in suture patterns and fiber end architecture.At 2 weeks, dystrophic lenses displayed an inverted Y suture on the posterior, and by 3 weeks most lenses had at least one sub-branch. Additional sub-branches were observed with time, opacities being visible as early as 4 weeks and progressing into PSC plaques by 6 weeks. Control lenses displayed inverted Y sutures at all ages and were transparent. SEM of dystrophic lenses revealed fiber ends with normal size, shape, arrangement, and filopodia at 2 weeks; scattered areas of dome-shaped fiber ends and small filopodia were present at 3 weeks. At 4 weeks the irregularly arranged domed fiber ends had extremely long filopodia with 'boutons' at their tips. By 6 weeks all fiber ends within plaques displayed rounded or domed basal membranes and lacked filopodial extensions. Control lenses at all time points had comparable ultrastructure to the 2 week old dystrophic lenses. F-actin arrangement within the basal membrane complex (BMC) of control lenses showed the expected peripheral pattern of labeling at all ages. Dystrophic RCS lenses at 2 weeks were comparable to controls, however by 3-4 weeks they displayed scattered foci of F-actin within the BMC. At all time points thereafter, F-actin was rearranged into a 'rosette' pattern of prominent foci at cell vertices.The data are consistent with the hypothesis that migration of basal fiber ends is altered in a two stage process wherein initially, migration patterns undergo a rapid shift resulting in abnormal suture sub-branch formation. Subsequent cytological alterations are consistent with an eventual cessation of migration, precluding proper targeting of basal ends to their sutural destinations and leading to cataract plaque formation.

Dataset Information

Effect of photoreceptor degeneration on circadian photoreception and free-running period in the Royal College of Surgeons rat.

Publications

Effect of photoreceptor degeneration on circadian photoreception and free-running period in the Royal College of Surgeons rat.

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