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Mature retinal pigment epithelium cells are retained in the cell cycle and proliferate in vivo.

Al-Hussaini H, Kam JH, Vugler A, Semo M, Jeffery G - Mol. Vis. (2008)

Bottom Line: These cells were negative for Caspase 3, hence were not apoptotic.Ki67-positive cells were also seen in human RPE.Further, many cells positive for BrdU were identified in similar retinal regions, confirming that RPE cells not only enter the cell cycle but also divide, albeit at a slow cell cycle rate.

View Article: PubMed Central - PubMed

Affiliation: Institute of Ophthalmology, University College London, London, United Kingdom.

ABSTRACT

Purpose: To investigate the capacity of mature retinal pigment epithelium (RPE) cells to enter the cell cycle in vivo using a range of RPE-specific and proliferative specific markers in both pigmented and albino rats.

Methods: Whole-mounted retinas of both Dark Agouti and albino rats were immunolabeled with cell cycle markers Ki67 or PCNA and double labeled with RPE cell marker RPE65 or CRALBP. The number and distribution of these cells was mapped. An additional group of Dark Agouti rats were given repeated intraperitoneal injections of Bromodeoxyuridine (BrdU )for 20 days and then sacrificed 30 days later. The retinas were then processed for BrdU detection and Otx, a RPE cell-specific marker. For comparison, human RPE tissue from a postmortem donor was also labeled for Ki67.

Results: In both pigmentation phenotypes, a subpopulation of mature RPE cells in the periphery were positive for both cell cycle markers. These cells were negative for Caspase 3, hence were not apoptotic. Ki67-positive cells were also seen in human RPE. Further, many cells positive for BrdU were identified in similar retinal regions, confirming that RPE cells not only enter the cell cycle but also divide, albeit at a slow cell cycle rate. There was a ten fold increase in the number of RPE cells positive for cell cycle markers in albino (approximately 200 cells) compared to pigmented rats (approximately 20 cells).

Conclusions: Peripheral RPE cells in rats have the capacity to enter the cell cycle and complete cellular division.

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Related in: MedlinePlus

The distribution and number of Ki67 positive RPE cells in the retinae of pigmented (black bars) and albino (blue bars) rats. A and B show the relative distribution of Ki67 cells in retinae of pigmented and albino rats. In both cases the largest percentage of the total number of cells are located in the periphery with none in central retina regions. The actual distribution of these cells in a pigmented rat is given in C. D shows the absolute number of Ki67 positive RPE cells in a pigmented and an albino animals. The differences shown in A and B between the different retinal regions were statistically significant (ANOVA p<0.0001). Differences between equatorial and peripheral regions were also statistically significant (Newman Keules p<0.001). While the relative differences in the distribution of Ki67 cells within retinae was similar between pigmentation phenotypes, there were always many more RPE cells labeled with Ki67 in albinos compared with pigmented rats. This difference was statistically significant (Newman-Keuls p<0.01).
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f2: The distribution and number of Ki67 positive RPE cells in the retinae of pigmented (black bars) and albino (blue bars) rats. A and B show the relative distribution of Ki67 cells in retinae of pigmented and albino rats. In both cases the largest percentage of the total number of cells are located in the periphery with none in central retina regions. The actual distribution of these cells in a pigmented rat is given in C. D shows the absolute number of Ki67 positive RPE cells in a pigmented and an albino animals. The differences shown in A and B between the different retinal regions were statistically significant (ANOVA p<0.0001). Differences between equatorial and peripheral regions were also statistically significant (Newman Keules p<0.001). While the relative differences in the distribution of Ki67 cells within retinae was similar between pigmentation phenotypes, there were always many more RPE cells labeled with Ki67 in albinos compared with pigmented rats. This difference was statistically significant (Newman-Keuls p<0.01).

Mentions: Ki67-labeled cells were only present in equatorial and peripheral regions (Figure 2). None were seen centrally, close to the optic nerve head. Negative controls in which all stages of immune processing were undertaken, except the application of the primary antibody, failed to show any label in the RPE in either central or peripheral locations with either Ki67 or PCNA. With the exception of cell numbers there were no geographic differences in the patterns of labeling found using either Ki67 or PCNA.


Mature retinal pigment epithelium cells are retained in the cell cycle and proliferate in vivo.

Al-Hussaini H, Kam JH, Vugler A, Semo M, Jeffery G - Mol. Vis. (2008)

The distribution and number of Ki67 positive RPE cells in the retinae of pigmented (black bars) and albino (blue bars) rats. A and B show the relative distribution of Ki67 cells in retinae of pigmented and albino rats. In both cases the largest percentage of the total number of cells are located in the periphery with none in central retina regions. The actual distribution of these cells in a pigmented rat is given in C. D shows the absolute number of Ki67 positive RPE cells in a pigmented and an albino animals. The differences shown in A and B between the different retinal regions were statistically significant (ANOVA p<0.0001). Differences between equatorial and peripheral regions were also statistically significant (Newman Keules p<0.001). While the relative differences in the distribution of Ki67 cells within retinae was similar between pigmentation phenotypes, there were always many more RPE cells labeled with Ki67 in albinos compared with pigmented rats. This difference was statistically significant (Newman-Keuls p<0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2562424&req=5

f2: The distribution and number of Ki67 positive RPE cells in the retinae of pigmented (black bars) and albino (blue bars) rats. A and B show the relative distribution of Ki67 cells in retinae of pigmented and albino rats. In both cases the largest percentage of the total number of cells are located in the periphery with none in central retina regions. The actual distribution of these cells in a pigmented rat is given in C. D shows the absolute number of Ki67 positive RPE cells in a pigmented and an albino animals. The differences shown in A and B between the different retinal regions were statistically significant (ANOVA p<0.0001). Differences between equatorial and peripheral regions were also statistically significant (Newman Keules p<0.001). While the relative differences in the distribution of Ki67 cells within retinae was similar between pigmentation phenotypes, there were always many more RPE cells labeled with Ki67 in albinos compared with pigmented rats. This difference was statistically significant (Newman-Keuls p<0.01).
Mentions: Ki67-labeled cells were only present in equatorial and peripheral regions (Figure 2). None were seen centrally, close to the optic nerve head. Negative controls in which all stages of immune processing were undertaken, except the application of the primary antibody, failed to show any label in the RPE in either central or peripheral locations with either Ki67 or PCNA. With the exception of cell numbers there were no geographic differences in the patterns of labeling found using either Ki67 or PCNA.

Bottom Line: These cells were negative for Caspase 3, hence were not apoptotic.Ki67-positive cells were also seen in human RPE.Further, many cells positive for BrdU were identified in similar retinal regions, confirming that RPE cells not only enter the cell cycle but also divide, albeit at a slow cell cycle rate.

View Article: PubMed Central - PubMed

Affiliation: Institute of Ophthalmology, University College London, London, United Kingdom.

ABSTRACT

Purpose: To investigate the capacity of mature retinal pigment epithelium (RPE) cells to enter the cell cycle in vivo using a range of RPE-specific and proliferative specific markers in both pigmented and albino rats.

Methods: Whole-mounted retinas of both Dark Agouti and albino rats were immunolabeled with cell cycle markers Ki67 or PCNA and double labeled with RPE cell marker RPE65 or CRALBP. The number and distribution of these cells was mapped. An additional group of Dark Agouti rats were given repeated intraperitoneal injections of Bromodeoxyuridine (BrdU )for 20 days and then sacrificed 30 days later. The retinas were then processed for BrdU detection and Otx, a RPE cell-specific marker. For comparison, human RPE tissue from a postmortem donor was also labeled for Ki67.

Results: In both pigmentation phenotypes, a subpopulation of mature RPE cells in the periphery were positive for both cell cycle markers. These cells were negative for Caspase 3, hence were not apoptotic. Ki67-positive cells were also seen in human RPE. Further, many cells positive for BrdU were identified in similar retinal regions, confirming that RPE cells not only enter the cell cycle but also divide, albeit at a slow cell cycle rate. There was a ten fold increase in the number of RPE cells positive for cell cycle markers in albino (approximately 200 cells) compared to pigmented rats (approximately 20 cells).

Conclusions: Peripheral RPE cells in rats have the capacity to enter the cell cycle and complete cellular division.

Show MeSH
Related in: MedlinePlus