Selective pericyte degeneration in the retinal capillaries of galactose-fed dogs results from apoptosis linked to aldose reductase-catalyzed galactitol accumulation

M. Murata, N. Ohta, S. Fujisawa, J. Y. Tsai, S. Sato, Y. Akagi, Y. Takahashi, H. Neuenschwander, Peter F Kador

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Galactose-fed dogs develop retinal capillary changes similar to diabetic retinopathy with pericyte degeneration as the initial lesion. This is followed by the formation of microaneurysms, hemorrhages, and some areas of acellularity. To investigate the mechanisms for selective pericyte degeneration, retinal capillary pericytes and endothelial cells isolated from beagle dog retina were cultured for 2 weeks in Dulbecco's modified Eagle's medium (DMEM) containing 50 mM D-galactose. Apoptosis was detected in pericytes but not endothelial cells by in situ terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick end labelling (TUNEL) staining and the DNA fragmentation assay on agarose gel electrophoresis. This apoptosis was prevented by the addition of the aldose reductase inhibitor AL 1576 to the culture medium containing galactose. Apoptosis was not observed when pericytes were similarly cultured in control DMEM medium. These data support the premise that the selective degeneration of retinal capillary pericytes observed in galactose-fed dogs is linked to increased aldose reductase activity in these cells.

Original languageEnglish (US)
Pages (from-to)363-370
Number of pages8
JournalJournal of Diabetes and Its Complications
Volume16
Issue number5
DOIs
StatePublished - Jan 1 2002

Fingerprint

Galactitol
Aldehyde Reductase
Pericytes
Retinal Degeneration
Galactose
Dogs
Apoptosis
Eagles
Endothelial Cells
DNA Nucleotidylexotransferase
Agar Gel Electrophoresis
In Situ Nick-End Labeling
Diabetic Retinopathy
DNA Fragmentation
Biotin
Culture Media
Retina
Staining and Labeling
Hemorrhage

Keywords

  • Aldose reductase
  • Apoptosis
  • Endothelial cells
  • Pericyte
  • Retinal capillary

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Selective pericyte degeneration in the retinal capillaries of galactose-fed dogs results from apoptosis linked to aldose reductase-catalyzed galactitol accumulation. / Murata, M.; Ohta, N.; Fujisawa, S.; Tsai, J. Y.; Sato, S.; Akagi, Y.; Takahashi, Y.; Neuenschwander, H.; Kador, Peter F.

In: Journal of Diabetes and Its Complications, Vol. 16, No. 5, 01.01.2002, p. 363-370.

Research output: Contribution to journalArticle

Murata, M. ; Ohta, N. ; Fujisawa, S. ; Tsai, J. Y. ; Sato, S. ; Akagi, Y. ; Takahashi, Y. ; Neuenschwander, H. ; Kador, Peter F. / Selective pericyte degeneration in the retinal capillaries of galactose-fed dogs results from apoptosis linked to aldose reductase-catalyzed galactitol accumulation. In: Journal of Diabetes and Its Complications. 2002 ; Vol. 16, No. 5. pp. 363-370.
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