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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

Proportion of senescent cells within primary HLECs from different ages. Representative pictures of primary HLECs from different ages are denoted by A, B, and C. Senescent HLECs were not observed in young samples (A) (<10 years), but they were observed and increased with age in B (50–60 years) (arrow) and C (>60 years) (arrow). D shows the quantified data which are presented as mean ± SEM (group 50–60 years, n = 12; group 60–80 years, n = 39; and group >80 years, n = 14). Scale bar, 40 μm. ∗P < 0.05 versus proportion of senescent HLECs from 50 to 60 years. HLEC = human lens epithelial cell, SEM = standard error of mean.
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Figure 3: Proportion of senescent cells within primary HLECs from different ages. Representative pictures of primary HLECs from different ages are denoted by A, B, and C. Senescent HLECs were not observed in young samples (A) (<10 years), but they were observed and increased with age in B (50–60 years) (arrow) and C (>60 years) (arrow). D shows the quantified data which are presented as mean ± SEM (group 50–60 years, n = 12; group 60–80 years, n = 39; and group >80 years, n = 14). Scale bar, 40 μm. ∗P < 0.05 versus proportion of senescent HLECs from 50 to 60 years. HLEC = human lens epithelial cell, SEM = standard error of mean.

Mentions: Interestingly, some HLECs from older people were observed to become larger, flatter, and irregular with massive vacuoles in the cytoplasm (referred to as senescent HLECs) during culturing, whereas others showed uniform rectangle morphologies, as in the samples from children. The representative images are shown in Fig. 3A–C. Moreover, the senescent HLECs stopped proliferating and gradually died afterwards. After being cultured for 3 weeks, the proportion of senescent cells were 10.67% ± 3.62% cells within the HELCs in group 1, and then it increased and reached 27.96% ± 2.05% in group 2 and 29.21% ± 4.86% in group 3 (Fig. 3D). These results indicate that the functions of HLECs in older individuals decline probably because senescent HLECs cannot be replenished due to the exhaustion of stem cell pools.


Effects of senescent lens epithelial cells on the severity of age-related cortical cataract in humans
Proportion of senescent cells within primary HLECs from different ages. Representative pictures of primary HLECs from different ages are denoted by A, B, and C. Senescent HLECs were not observed in young samples (A) (<10 years), but they were observed and increased with age in B (50–60 years) (arrow) and C (>60 years) (arrow). D shows the quantified data which are presented as mean ± SEM (group 50–60 years, n = 12; group 60–80 years, n = 39; and group >80 years, n = 14). Scale bar, 40 μm. ∗P < 0.05 versus proportion of senescent HLECs from 50 to 60 years. HLEC = human lens epithelial cell, SEM = standard error of mean.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Proportion of senescent cells within primary HLECs from different ages. Representative pictures of primary HLECs from different ages are denoted by A, B, and C. Senescent HLECs were not observed in young samples (A) (<10 years), but they were observed and increased with age in B (50–60 years) (arrow) and C (>60 years) (arrow). D shows the quantified data which are presented as mean ± SEM (group 50–60 years, n = 12; group 60–80 years, n = 39; and group >80 years, n = 14). Scale bar, 40 μm. ∗P < 0.05 versus proportion of senescent HLECs from 50 to 60 years. HLEC = human lens epithelial cell, SEM = standard error of mean.
Mentions: Interestingly, some HLECs from older people were observed to become larger, flatter, and irregular with massive vacuoles in the cytoplasm (referred to as senescent HLECs) during culturing, whereas others showed uniform rectangle morphologies, as in the samples from children. The representative images are shown in Fig. 3A–C. Moreover, the senescent HLECs stopped proliferating and gradually died afterwards. After being cultured for 3 weeks, the proportion of senescent cells were 10.67% ± 3.62% cells within the HELCs in group 1, and then it increased and reached 27.96% ± 2.05% in group 2 and 29.21% ± 4.86% in group 3 (Fig. 3D). These results indicate that the functions of HLECs in older individuals decline probably because senescent HLECs cannot be replenished due to the exhaustion of stem cell pools.

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