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Abnormal fiber end migration in Royal College of Surgeons rats during posterior subcapsular cataract formation.

Joy A, Mohammed TA, Al-Ghoul KJ - Mol. Vis. (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, Rush University Medical Center, 600 S. Paulina St., Chicago, IL 60612, USA.

ABSTRACT

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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Related in: MedlinePlus

Graphical representation of increase in lens equatorial diameter with age in the dystrophic RCS/Lav lenses and control RCS-rdy+/Lav lenses. Lens size increased with age and there was a significant difference in equatorial diameter between the dystrophic and control lenses at 7–8 weeks postnatal (p<0.05).
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f1: Graphical representation of increase in lens equatorial diameter with age in the dystrophic RCS/Lav lenses and control RCS-rdy+/Lav lenses. Lens size increased with age and there was a significant difference in equatorial diameter between the dystrophic and control lenses at 7–8 weeks postnatal (p<0.05).

Mentions: The RCS/Lav rat lenses gradually increased in size (equatorial diameter) with age from an average of 2.96 mm at 2–3 weeks of age to 3.43 mm at 4–6 weeks of age and 3.76 mm by 7–8 weeks post natal, while the control RCS-rdy+/Lav lenses showed an average increase from 3.30 mm at 2–3 weeks, 4 mm at 4–6 weeks, and 4.51 mm at 7–8 weeks of age (Figure 1). In general, the control lenses were larger than the dystrophic lenses and after 4–6 weeks postnatal there was a significant pause in lens growth (equatorial diameter) in the RCS/Lav lenses. Statistical comparison showed that at 7–8 weeks, the dystrophic lenses were significantly smaller than the controls (p<0.05).


Abnormal fiber end migration in Royal College of Surgeons rats during posterior subcapsular cataract formation.

Joy A, Mohammed TA, Al-Ghoul KJ - Mol. Vis. (2010)

Graphical representation of increase in lens equatorial diameter with age in the dystrophic RCS/Lav lenses and control RCS-rdy+/Lav lenses. Lens size increased with age and there was a significant difference in equatorial diameter between the dystrophic and control lenses at 7–8 weeks postnatal (p<0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2925909&req=5

f1: Graphical representation of increase in lens equatorial diameter with age in the dystrophic RCS/Lav lenses and control RCS-rdy+/Lav lenses. Lens size increased with age and there was a significant difference in equatorial diameter between the dystrophic and control lenses at 7–8 weeks postnatal (p<0.05).
Mentions: The RCS/Lav rat lenses gradually increased in size (equatorial diameter) with age from an average of 2.96 mm at 2–3 weeks of age to 3.43 mm at 4–6 weeks of age and 3.76 mm by 7–8 weeks post natal, while the control RCS-rdy+/Lav lenses showed an average increase from 3.30 mm at 2–3 weeks, 4 mm at 4–6 weeks, and 4.51 mm at 7–8 weeks of age (Figure 1). In general, the control lenses were larger than the dystrophic lenses and after 4–6 weeks postnatal there was a significant pause in lens growth (equatorial diameter) in the RCS/Lav lenses. Statistical comparison showed that at 7–8 weeks, the dystrophic lenses were significantly smaller than the controls (p<0.05).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, Rush University Medical Center, 600 S. Paulina St., Chicago, IL 60612, USA.

ABSTRACT

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus