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Comparison of telomere length and association with progenitor cell markers in lacrimal gland between Sjögren syndrome and non-Sjögren syndrome dry eye patients.

Kawashima M, Kawakita T, Maida Y, Kamoi M, Ogawa Y, Shimmura S, Masutomi K, Tsubota K - Mol. Vis. (2011)

Bottom Line: Immunostaining for p63, nucleostemin, ATP-binding cassette, sub-family G, member 2 (ABCG2), and nestin was also performed.Among the samples from the non-Sjögren syndrome group, immunostaining revealed that p63 was expressed in 1-3 acinar cells in each acinar unit and continuously in the basal layer of duct cells.The results of this study indicate that 1) telo-FISH is a viable method of assessing telomere length in lacrimal gland, and 2) telomere length in Sjögren syndrome is shorter and associated with lower levels of expression of p63 and nucleostemin than in non-Sjögren syndrome.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

ABSTRACT

Purpose: Indicators of aging such as disruption of telomeric function due to shortening may be more frequent in dysfunctional lacrimal gland. The aims of this study were to 1) determine the viability of quantitative fluorescence in situ hybridization of telomeres (telo-FISH) for the assessment of telomere length in lacrimal gland in Sjögren and non- Sjögren syndrome patients; and 2) investigate the relationship between progenitor cell markers and telomere length in both groups.

Methods: Quantitative fluorescence in situ hybridization with a peptide nucleic acid probe complementary to the telomere repeat sequence was performed on frozen sections from human lacrimal gland tissues. The mean fluorescence intensity of telomere spots was automatically quantified by image analysis as relative telomere length in lacrimal gland epithelial cells. Immunostaining for p63, nucleostemin, ATP-binding cassette, sub-family G, member 2 (ABCG2), and nestin was also performed.

Results: Telomere intensity in the Sjögren syndrome group (6,785.0±455) was significantly lower than that in the non-Sjögren syndrome group (7,494.7±477; p=0.02). Among the samples from the non-Sjögren syndrome group, immunostaining revealed that p63 was expressed in 1-3 acinar cells in each acinar unit and continuously in the basal layer of duct cells. In contrast, in the Sjögren syndrome group, p63 and nucleostemin showed a lower level of expression. ABCG2 was expressed in acinar cells in both sjogren and non-Sjogren syndrome.

Conclusions: The results of this study indicate that 1) telo-FISH is a viable method of assessing telomere length in lacrimal gland, and 2) telomere length in Sjögren syndrome is shorter and associated with lower levels of expression of p63 and nucleostemin than in non-Sjögren syndrome.

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Telomere shortening in Sjögren syndrome. Representative telo-FISH photograph of non-Sjögren syndrome (A) and Sjögren syndrome (B) lacrimal glands. Scatter plot of age and telomere intensity (TI; C). Comparison of average telomere intensity in Sjögren and non-Sjögren syndrome groups demonstrated that telomeres were significantly shorter in Sjögren syndrome group (D; p=0.02).
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f1: Telomere shortening in Sjögren syndrome. Representative telo-FISH photograph of non-Sjögren syndrome (A) and Sjögren syndrome (B) lacrimal glands. Scatter plot of age and telomere intensity (TI; C). Comparison of average telomere intensity in Sjögren and non-Sjögren syndrome groups demonstrated that telomeres were significantly shorter in Sjögren syndrome group (D; p=0.02).

Mentions: Large numbers of inflammatory cells invade lacrimal gland tissue in Sjögren syndrome. Therefore, we selected only locations where acinar unit structure was well preserved for telo-FISH. In this study, telo-FISH was successfully performed on fixed frozen tissue sections. Representative photos are shown in Figure 1A,B. High levels of Cy3 expression were observed in the nuclei in lacrimal gland in the non-Sjögren syndrome group, whereas expression was weak in the Sjögren syndrome group (Figure 1A,B). Telomere intensity in lacrimal gland epithelial cells in the Sjögren syndrome group (6,785.0±455) was significantly lower than that in the non-Sjögren syndrome group (7,494.7±477; p=0.02, Figure 1C,D).


Comparison of telomere length and association with progenitor cell markers in lacrimal gland between Sjögren syndrome and non-Sjögren syndrome dry eye patients.

Kawashima M, Kawakita T, Maida Y, Kamoi M, Ogawa Y, Shimmura S, Masutomi K, Tsubota K - Mol. Vis. (2011)

Telomere shortening in Sjögren syndrome. Representative telo-FISH photograph of non-Sjögren syndrome (A) and Sjögren syndrome (B) lacrimal glands. Scatter plot of age and telomere intensity (TI; C). Comparison of average telomere intensity in Sjögren and non-Sjögren syndrome groups demonstrated that telomeres were significantly shorter in Sjögren syndrome group (D; p=0.02).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108899&req=5

f1: Telomere shortening in Sjögren syndrome. Representative telo-FISH photograph of non-Sjögren syndrome (A) and Sjögren syndrome (B) lacrimal glands. Scatter plot of age and telomere intensity (TI; C). Comparison of average telomere intensity in Sjögren and non-Sjögren syndrome groups demonstrated that telomeres were significantly shorter in Sjögren syndrome group (D; p=0.02).
Mentions: Large numbers of inflammatory cells invade lacrimal gland tissue in Sjögren syndrome. Therefore, we selected only locations where acinar unit structure was well preserved for telo-FISH. In this study, telo-FISH was successfully performed on fixed frozen tissue sections. Representative photos are shown in Figure 1A,B. High levels of Cy3 expression were observed in the nuclei in lacrimal gland in the non-Sjögren syndrome group, whereas expression was weak in the Sjögren syndrome group (Figure 1A,B). Telomere intensity in lacrimal gland epithelial cells in the Sjögren syndrome group (6,785.0±455) was significantly lower than that in the non-Sjögren syndrome group (7,494.7±477; p=0.02, Figure 1C,D).

Bottom Line: Immunostaining for p63, nucleostemin, ATP-binding cassette, sub-family G, member 2 (ABCG2), and nestin was also performed.Among the samples from the non-Sjögren syndrome group, immunostaining revealed that p63 was expressed in 1-3 acinar cells in each acinar unit and continuously in the basal layer of duct cells.The results of this study indicate that 1) telo-FISH is a viable method of assessing telomere length in lacrimal gland, and 2) telomere length in Sjögren syndrome is shorter and associated with lower levels of expression of p63 and nucleostemin than in non-Sjögren syndrome.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

ABSTRACT

Purpose: Indicators of aging such as disruption of telomeric function due to shortening may be more frequent in dysfunctional lacrimal gland. The aims of this study were to 1) determine the viability of quantitative fluorescence in situ hybridization of telomeres (telo-FISH) for the assessment of telomere length in lacrimal gland in Sjögren and non- Sjögren syndrome patients; and 2) investigate the relationship between progenitor cell markers and telomere length in both groups.

Methods: Quantitative fluorescence in situ hybridization with a peptide nucleic acid probe complementary to the telomere repeat sequence was performed on frozen sections from human lacrimal gland tissues. The mean fluorescence intensity of telomere spots was automatically quantified by image analysis as relative telomere length in lacrimal gland epithelial cells. Immunostaining for p63, nucleostemin, ATP-binding cassette, sub-family G, member 2 (ABCG2), and nestin was also performed.

Results: Telomere intensity in the Sjögren syndrome group (6,785.0±455) was significantly lower than that in the non-Sjögren syndrome group (7,494.7±477; p=0.02). Among the samples from the non-Sjögren syndrome group, immunostaining revealed that p63 was expressed in 1-3 acinar cells in each acinar unit and continuously in the basal layer of duct cells. In contrast, in the Sjögren syndrome group, p63 and nucleostemin showed a lower level of expression. ABCG2 was expressed in acinar cells in both sjogren and non-Sjogren syndrome.

Conclusions: The results of this study indicate that 1) telo-FISH is a viable method of assessing telomere length in lacrimal gland, and 2) telomere length in Sjögren syndrome is shorter and associated with lower levels of expression of p63 and nucleostemin than in non-Sjögren syndrome.

Show MeSH
Related in: MedlinePlus