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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 percentage of binucleated RPE cells in different retinal regions in pigmented (black bars) and albino (blue bars) rats. In adult rodent retinas, many of the RPE cells were binucleated. The proportion of these have been determined in both pigmented (A) and albino (B) retinas. The retinas were divided into three roughly equal geographic regions: central, equatorial, and peripheral. In both pigmentation phenotypes the majority of the binucleated cells were located toward the central retina, although many were also found in equatorial regions. The distribution of these cells is the reverse pattern of that found for Ki67-positive cells shown in Figure 2. The differences in A and B are statistically significant (ANOVA, p<0.001). In both cases, the differences between the percentage of binucleated RPE cells between central and equatorial regions were not statistically significant. However, differences in the percentage of binucleated RPE cells found central and peripheral regions were significantly different (Newman-Keuls p<0.01). The differences between equatorial and peripheral regions were also statistically significant (Newman-Keuls p<0.01).
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f4: The percentage of binucleated RPE cells in different retinal regions in pigmented (black bars) and albino (blue bars) rats. In adult rodent retinas, many of the RPE cells were binucleated. The proportion of these have been determined in both pigmented (A) and albino (B) retinas. The retinas were divided into three roughly equal geographic regions: central, equatorial, and peripheral. In both pigmentation phenotypes the majority of the binucleated cells were located toward the central retina, although many were also found in equatorial regions. The distribution of these cells is the reverse pattern of that found for Ki67-positive cells shown in Figure 2. The differences in A and B are statistically significant (ANOVA, p<0.001). In both cases, the differences between the percentage of binucleated RPE cells between central and equatorial regions were not statistically significant. However, differences in the percentage of binucleated RPE cells found central and peripheral regions were significantly different (Newman-Keuls p<0.01). The differences between equatorial and peripheral regions were also statistically significant (Newman-Keuls p<0.01).

Mentions: During the first two postnatal weeks, after cell production in the rodent RPE is largely complete, some RPE cells undergo nuclear division. This does not translate into full cell division, leaving a cellular population that is largely binucleated. The relative distribution of these cells has not been recorded [18]. Figure 4 shows the distribution of binucleated cells in pigmented and albino rat retinas that have been divided into central, equatorial, and peripheral regions. In both cases it is clear that the majority of binucleated cells are located in the central retina, with many spilling over into equatorial regions, but with relatively few in the periphery. RPE cells in central regions could also contain more than two nuclei. The small population of binucleated cells in the periphery were not obviously biased toward areas within this region adjacent to the equatorial sector. Hence, the distribution of binucleated cells was separate, although partly overlapping with that of the Ki67-positive cell population.


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 percentage of binucleated RPE cells in different retinal regions in pigmented (black bars) and albino (blue bars) rats. In adult rodent retinas, many of the RPE cells were binucleated. The proportion of these have been determined in both pigmented (A) and albino (B) retinas. The retinas were divided into three roughly equal geographic regions: central, equatorial, and peripheral. In both pigmentation phenotypes the majority of the binucleated cells were located toward the central retina, although many were also found in equatorial regions. The distribution of these cells is the reverse pattern of that found for Ki67-positive cells shown in Figure 2. The differences in A and B are statistically significant (ANOVA, p<0.001). In both cases, the differences between the percentage of binucleated RPE cells between central and equatorial regions were not statistically significant. However, differences in the percentage of binucleated RPE cells found central and peripheral regions were significantly different (Newman-Keuls p<0.01). The differences between equatorial and peripheral regions were also 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

f4: The percentage of binucleated RPE cells in different retinal regions in pigmented (black bars) and albino (blue bars) rats. In adult rodent retinas, many of the RPE cells were binucleated. The proportion of these have been determined in both pigmented (A) and albino (B) retinas. The retinas were divided into three roughly equal geographic regions: central, equatorial, and peripheral. In both pigmentation phenotypes the majority of the binucleated cells were located toward the central retina, although many were also found in equatorial regions. The distribution of these cells is the reverse pattern of that found for Ki67-positive cells shown in Figure 2. The differences in A and B are statistically significant (ANOVA, p<0.001). In both cases, the differences between the percentage of binucleated RPE cells between central and equatorial regions were not statistically significant. However, differences in the percentage of binucleated RPE cells found central and peripheral regions were significantly different (Newman-Keuls p<0.01). The differences between equatorial and peripheral regions were also statistically significant (Newman-Keuls p<0.01).
Mentions: During the first two postnatal weeks, after cell production in the rodent RPE is largely complete, some RPE cells undergo nuclear division. This does not translate into full cell division, leaving a cellular population that is largely binucleated. The relative distribution of these cells has not been recorded [18]. Figure 4 shows the distribution of binucleated cells in pigmented and albino rat retinas that have been divided into central, equatorial, and peripheral regions. In both cases it is clear that the majority of binucleated cells are located in the central retina, with many spilling over into equatorial regions, but with relatively few in the periphery. RPE cells in central regions could also contain more than two nuclei. The small population of binucleated cells in the periphery were not obviously biased toward areas within this region adjacent to the equatorial sector. Hence, the distribution of binucleated cells was separate, although partly overlapping with that of the Ki67-positive cell population.

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