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Effects of senescent lens epithelial cells on the severity of age-related cortical cataract in humans

View Article: PubMed Central - PubMed

ABSTRACT

The aging of lens progenitor cell has been repeatedly proposed to play a key role in age-related cataracts (ARCs), but the mechanism is far from being understood. The present study aims to investigate the relationship between aging of lens progenitor/epithelial cells and the 4 subtypes of ARCs in humans.

Lens capsules, which were collected from ARC patients during surgery, were divided into 3 groups according to the age of patients (50–60, 60–80, and >80 years). The expressions of lens progenitor cell-related markers Sox2, Abcg2, and Ki67 were first examined in human lens epithelial cells (HLECs) in situ. Then, the percentage of senescent and SA-β-gal+ HLECs isolated from lens capsules were quantified. Finally, the potential relationships between the percentage of senescent (and SA-β-gal+) HLECs and the severity of ARCs were analyzed.

Ki67+, Sox2+, and Abcg2+ HLECs in lens capsules were clearly more abundant in young people than in patients older than 50 years, and they were almost absent in patients older than 60 years. The percentage of primary HLECs with aging morphology increased with age, consistent with the results of SA-β-gal+ primary HLECs. Only cortical cataract classification was found to be strongly related to the percentage of SA-β-gal+ and senescent HLECs.

Our study gave the initial evidence on the dynamical change of lens stem/progenitor cells in human lens capsule with age and suggested that lens progenitor/epithelial cell aging is important in the severity of cortical cataracts.

No MeSH data available.


Related in: MedlinePlus

Expressions of Ki67, Sox2, and Abcg2 in lens capsules from patients. Ki67+, Sox2+, and Abcg2+ cells were observed in the lens capsules from young people (A, D, G), but they were reduced in the lens capsules from older patients. Eventually, Ki67 (red) signaling could not be detected in the samples from patients older than 50 years (B, C), and Sox2 (red) and Abcg2 (green) signaling was absent in the samples from patients older than 60 years (E, F, H, I). J–L show the quantified data which are presented as mean ± SEM (group <10 years, n = 5; group 50–60 years, n = 5; and group >60 years, n = 5). Scale bar, 40 μm. ∗P < 0.05 and ∗∗P < 0.01 versus proportion of Ki67+, Sox2+, or Abcg2+ HLECs from <10 years. HLEC = human lens epithelial cell, ND = not detected, SEM = standard error of mean.
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Figure 1: Expressions of Ki67, Sox2, and Abcg2 in lens capsules from patients. Ki67+, Sox2+, and Abcg2+ cells were observed in the lens capsules from young people (A, D, G), but they were reduced in the lens capsules from older patients. Eventually, Ki67 (red) signaling could not be detected in the samples from patients older than 50 years (B, C), and Sox2 (red) and Abcg2 (green) signaling was absent in the samples from patients older than 60 years (E, F, H, I). J–L show the quantified data which are presented as mean ± SEM (group <10 years, n = 5; group 50–60 years, n = 5; and group >60 years, n = 5). Scale bar, 40 μm. ∗P < 0.05 and ∗∗P < 0.01 versus proportion of Ki67+, Sox2+, or Abcg2+ HLECs from <10 years. HLEC = human lens epithelial cell, ND = not detected, SEM = standard error of mean.

Mentions: A total of 190 anterior lens capsules from ARC patients were divided into 3 groups with age: group 1 (50–60 years), group 2 (60–80 years), and group 3 (>80 years). Details are presented in Table 1. One of the hypotheses for ARC is senescent and exhaustion of LSCs in lens capsules.[10] Therefore, the expressions of lens stem cell markers Sox2, Ki67, and Abcg2 in situ were first examined through immunofluorescence. A large amount of Ki67+ cells were found in the lens capsules from children aged 0 to 10 years, while they were almost absent in the lens capsules from patients older than 50 years. This finding suggests that LECs gradually lose their proliferation ability with age (Fig. 1A–C, J). Sox2 and Abcg2 were found to express in many kinds of stem cells, such as embryonic stem cells and neural stem cells, among others.[16,17] In our study, the number of Sox2+ and Abcg2+ gradually decreased, and they were not observed within HLECs from patients older than 60 years. This finding indicates the exhaustion of stem cell pool within HLECs (Fig. 1D–L).


Effects of senescent lens epithelial cells on the severity of age-related cortical cataract in humans
Expressions of Ki67, Sox2, and Abcg2 in lens capsules from patients. Ki67+, Sox2+, and Abcg2+ cells were observed in the lens capsules from young people (A, D, G), but they were reduced in the lens capsules from older patients. Eventually, Ki67 (red) signaling could not be detected in the samples from patients older than 50 years (B, C), and Sox2 (red) and Abcg2 (green) signaling was absent in the samples from patients older than 60 years (E, F, H, I). J–L show the quantified data which are presented as mean ± SEM (group <10 years, n = 5; group 50–60 years, n = 5; and group >60 years, n = 5). Scale bar, 40 μm. ∗P < 0.05 and ∗∗P < 0.01 versus proportion of Ki67+, Sox2+, or Abcg2+ HLECs from <10 years. HLEC = human lens epithelial cell, ND = not detected, SEM = standard error of mean.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998311&req=5

Figure 1: Expressions of Ki67, Sox2, and Abcg2 in lens capsules from patients. Ki67+, Sox2+, and Abcg2+ cells were observed in the lens capsules from young people (A, D, G), but they were reduced in the lens capsules from older patients. Eventually, Ki67 (red) signaling could not be detected in the samples from patients older than 50 years (B, C), and Sox2 (red) and Abcg2 (green) signaling was absent in the samples from patients older than 60 years (E, F, H, I). J–L show the quantified data which are presented as mean ± SEM (group <10 years, n = 5; group 50–60 years, n = 5; and group >60 years, n = 5). Scale bar, 40 μm. ∗P < 0.05 and ∗∗P < 0.01 versus proportion of Ki67+, Sox2+, or Abcg2+ HLECs from <10 years. HLEC = human lens epithelial cell, ND = not detected, SEM = standard error of mean.
Mentions: A total of 190 anterior lens capsules from ARC patients were divided into 3 groups with age: group 1 (50–60 years), group 2 (60–80 years), and group 3 (>80 years). Details are presented in Table 1. One of the hypotheses for ARC is senescent and exhaustion of LSCs in lens capsules.[10] Therefore, the expressions of lens stem cell markers Sox2, Ki67, and Abcg2 in situ were first examined through immunofluorescence. A large amount of Ki67+ cells were found in the lens capsules from children aged 0 to 10 years, while they were almost absent in the lens capsules from patients older than 50 years. This finding suggests that LECs gradually lose their proliferation ability with age (Fig. 1A–C, J). Sox2 and Abcg2 were found to express in many kinds of stem cells, such as embryonic stem cells and neural stem cells, among others.[16,17] In our study, the number of Sox2+ and Abcg2+ gradually decreased, and they were not observed within HLECs from patients older than 60 years. This finding indicates the exhaustion of stem cell pool within HLECs (Fig. 1D–L).

View Article: PubMed Central - PubMed

ABSTRACT

The aging of lens progenitor cell has been repeatedly proposed to play a key role in age-related cataracts (ARCs), but the mechanism is far from being understood. The present study aims to investigate the relationship between aging of lens progenitor/epithelial cells and the 4 subtypes of ARCs in humans.

Lens capsules, which were collected from ARC patients during surgery, were divided into 3 groups according to the age of patients (50&ndash;60, 60&ndash;80, and &gt;80 years). The expressions of lens progenitor cell-related markers Sox2, Abcg2, and Ki67 were first examined in human lens epithelial cells (HLECs) in situ. Then, the percentage of senescent and SA-&beta;-gal+ HLECs isolated from lens capsules were quantified. Finally, the potential relationships between the percentage of senescent (and SA-&beta;-gal+) HLECs and the severity of ARCs were analyzed.

Ki67+, Sox2+, and Abcg2+ HLECs in lens capsules were clearly more abundant in young people than in patients older than 50 years, and they were almost absent in patients older than 60 years. The percentage of primary HLECs with aging morphology increased with age, consistent with the results of SA-&beta;-gal+ primary HLECs. Only cortical cataract classification was found to be strongly related to the percentage of SA-&beta;-gal+ and senescent HLECs.

Our study gave the initial evidence on the dynamical change of lens stem/progenitor cells in human lens capsule with age and suggested that lens progenitor/epithelial cell aging is important in the severity of cortical cataracts.

No MeSH data available.


Related in: MedlinePlus