Selective pericyte degeneration in the retinal capillaries of galactose-fed dogs results from apoptosis linked to aldose reductase-catalyzed galactitol accumulation.
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.
Laboratory of Ocular Therapeutics, National Eye Institute, National Institutes of Health, Building 10, Room 10B11, 10 Center Drive, MSC 1850, Bethesda, MD 20892-1850, USA.
M
M
Murata
N
N
Ohta
S
S
Fujisawa
J-Y
JY
Tsai
S
S
Sato
Y
Y
Akagi
Y
Y
Takahashi
H
H
Neuenschwander
P F
PF
Kador
D000449:Aldehyde Reductase / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002196:Capillaries / Q000187:drug effects / Q000473:pathology*; D002478:Cells, Cultured; D004285:Dogs; D004376:Galactitol / Q000378:metabolism*; D005690:Galactose / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012171:Retinal Vessels / Q000187:drug effects* / Q000473:pathology
D004376:Galactitol; D000449:Aldehyde Reductase; D005690:Galactose