Glycogen storage in the human retinal pigment epithelium: a comparative study of diabetic and non-diabetic donors.
Liver and muscle glycogen content is reduced in diabetic patients but there is no information on the effect of diabetes on the glycogen content in the retinal pigment epithelium (RPE). The main aim of the study was to compare the glycogen content in the RPE between diabetic and non-diabetic human donors. Glycogen synthase (GS) and glycogen phosphorylase (GP), the key enzymes of glycogen metabolism, as well as their isoforms, were also assessed. For this purpose, 44 human postmortem eye cups were included (22 from 11 type 2 diabetic and 22 from 11 non-diabetic donors matched by age). Human RPE cells cultured in normoglycemic and hyperglycemic conditions were also analyzed. Glycogen content as well as the mRNA, protein content and enzyme activity of GS and GP were determined. In addition, GS and GP isoforms were characterized. In the RPE from diabetic donors, as well as in RPE cells grown in hyperglycemic conditions, the glycogen content was increased. The increase in glycogen content was associated with an increase in GS without changes in GP levels. In RPE form human donors, the muscle GS isoform but not the liver GS isoform was detected. Regarding GP, the muscle and brain isoform of GP but not the liver GP isoform were detected. We conclude that glycogen storage is increased in the RPE of diabetic patients, and it is associated with an increase in GS activity. Further studies aimed at determining the role of glycogen deposits in the pathogenesis of diabetic retinopathy are warranted.
Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain, cristina.hernandez@vhir.org.
Cristina
C
Hernández
Marta
M
Garcia-Ramírez
Mar
M
García-Rocha
Cristina
C
Saez-López
Ángela M
ÁM
Valverde
Joan J
JJ
Guinovart
Rafael
R
Simó
D000368:Aged; D000369:Aged, 80 and over; D003920:Diabetes Mellitus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006003:Glycogen / Q000378:metabolism*; D024981:Glycogen Phosphorylase / Q000235:genetics / Q000378:metabolism; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000201:enzymology / Q000378:metabolism*; D014019:Tissue Donors
D006003:Glycogen; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase