Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes

Keiji Naruse, J. Nakamura, Y. Hamada, M. Nakayama, S. Chaya, T. Komori, K. Kato, Y. Kasuya, K. Miwa, K. Naruse, N. Hotta

Research output: Contribution to journalArticle

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Abstract

The pathogenesis of pericyte loss, an initial deficit in the early stage of diabetic retinopathy, remains unclear. Polyol pathway hyperactivity has been implicated in the pathogenesis of diabetic retinopathy, and recent studies have suggested that apoptosis may be involved in pericyte loss. The present study was conducted to investigate whether high glucose induces apoptosis in cultured bovine retinal pericytes. The effect of an aldose reductase inhibitor, SNK-860, was also examined. After a 5 day incubation with various concentrations of glucose (5.5-40 mM) in the presence or absence of SNK-860, the cell viability and the percentages of dead cells were measured, and staining with the TUNEL method and Hoechst 33342, and DNA electrophoresis were performed. High glucose reduced the viability and increased the percentages of dead cells. TUNEL-positive cells were observed in pericytes under high glucose, but not in those under 5.5 mM glucose. In the staining of nuclei with Hoechst 33342, the percentage of apoptotic cells in total cells counted under high glucose was higher than that under 5.5 mM glucose. DNA electrophoresis of pericytes cultured with high glucose demonstrated a 'ladder pattern'. Hyperosmolarity also induced apoptosis in pericytes, but less than that by high glucose. SNK-860 inhibited the glucose-induced apoptosis in pericytes. These observations suggest that the pericyte loss in diabetic retinopathy involves an apoptotic process, and that the polyol pathway hyperactivity plays an important role in inducing apoptosis in pericytes by high glucose. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)309-315
Number of pages7
JournalExperimental Eye Research
Volume71
Issue number3
DOIs
Publication statusPublished - 2000
Externally publishedYes

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Aldehyde Reductase
Pericytes
Apoptosis
Glucose
Diabetic Retinopathy
In Situ Nick-End Labeling
Electrophoresis
Staining and Labeling
DNA
Cell Survival

Keywords

  • Aldose reductase inhibitor
  • Apoptosis
  • Diabetic retinopathy
  • High glucose
  • Polyol pathway
  • Retinal pericytes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes. / Naruse, Keiji; Nakamura, J.; Hamada, Y.; Nakayama, M.; Chaya, S.; Komori, T.; Kato, K.; Kasuya, Y.; Miwa, K.; Naruse, K.; Hotta, N.

In: Experimental Eye Research, Vol. 71, No. 3, 2000, p. 309-315.

Research output: Contribution to journalArticle

Naruse, K, Nakamura, J, Hamada, Y, Nakayama, M, Chaya, S, Komori, T, Kato, K, Kasuya, Y, Miwa, K, Naruse, K & Hotta, N 2000, 'Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes', Experimental Eye Research, vol. 71, no. 3, pp. 309-315. https://doi.org/10.1006/exer.2000.0882
Naruse, Keiji ; Nakamura, J. ; Hamada, Y. ; Nakayama, M. ; Chaya, S. ; Komori, T. ; Kato, K. ; Kasuya, Y. ; Miwa, K. ; Naruse, K. ; Hotta, N. / Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes. In: Experimental Eye Research. 2000 ; Vol. 71, No. 3. pp. 309-315.
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AB - The pathogenesis of pericyte loss, an initial deficit in the early stage of diabetic retinopathy, remains unclear. Polyol pathway hyperactivity has been implicated in the pathogenesis of diabetic retinopathy, and recent studies have suggested that apoptosis may be involved in pericyte loss. The present study was conducted to investigate whether high glucose induces apoptosis in cultured bovine retinal pericytes. The effect of an aldose reductase inhibitor, SNK-860, was also examined. After a 5 day incubation with various concentrations of glucose (5.5-40 mM) in the presence or absence of SNK-860, the cell viability and the percentages of dead cells were measured, and staining with the TUNEL method and Hoechst 33342, and DNA electrophoresis were performed. High glucose reduced the viability and increased the percentages of dead cells. TUNEL-positive cells were observed in pericytes under high glucose, but not in those under 5.5 mM glucose. In the staining of nuclei with Hoechst 33342, the percentage of apoptotic cells in total cells counted under high glucose was higher than that under 5.5 mM glucose. DNA electrophoresis of pericytes cultured with high glucose demonstrated a 'ladder pattern'. Hyperosmolarity also induced apoptosis in pericytes, but less than that by high glucose. SNK-860 inhibited the glucose-induced apoptosis in pericytes. These observations suggest that the pericyte loss in diabetic retinopathy involves an apoptotic process, and that the polyol pathway hyperactivity plays an important role in inducing apoptosis in pericytes by high glucose. (C) 2000 Academic Press.

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