Structural alterations of the erythrocyte membrane proteins in diabetic retinopathy.
BACKGROUND
Several rheological disorders of the erythrocytes, such as increased aggregation and decreased deformability, have been observed in diabetes mellitus and have been implicated in the development of diabetic microangiopathy. Structural alterations of the erythrocyte membrane proteins caused by the diabetic process may be at the origin of those observations. In the present study, we searched for erythrocyte membrane protein alterations in diabetic retinopathy.


METHODS
We examined peripheral blood samples from 40 type-2 diabetic patients with diabetic retinopathy of variable severity (19 males and 21 females, mean age 66.8 years, Group A) and we compared them with samples from 19 type-2 diabetic patients without diabetic retinopathy (13 males and six females, mean age 66.5 years, Group B) and 16 healthy volunteers (eight males and eight females, mean age 65.6 years, Group C). Erythrocyte membrane ghosts from all samples were subjected to SDS-PAGE, and the electrophoretic pattern of transmembrane and cytoskeletal proteins was analysed for each sample. The protein quantification of each electrophoretic band was accomplished through scanning densitometry.


RESULTS
No significant deviations from normal electrophoresis were observed in Groups B and C, apart from an increase in band 8 in two samples from Group B (11%). In contrast, in 14 samples from Group A (35%) we detected increases in protein band 8 and/or membrane-bound haemoglobin along with a decrease in spectrin. Moreover, increased mobility of band 3, an aberrant high molecular weight (MW) (> 255 kDa) band and a low MW (42 kDa) band were evident in ten samples from Group A (25%). Glycophorins were altered in 46% of Group-A patients versus 38% of Group-B patients. Females and patients with long duration of diabetes presented more electrophoretic abnormalities.


CONCLUSIONS
Structural alterations of the erythrocyte membrane proteins are shown for the first time in association with diabetic retinopathy. Their detection may serve as a blood marker for the development of diabetic microangiopathy. Further studies are needed to assess whether pharmaceutical intervention to the rheology of erythrocytes can prevent or alleviate microvascular diabetic complications.
Petropoulos
Ioannis K
IK
Department of Ophthalmology, University Hospitals of Geneva, 22 Alcide-Jentzer Street, 1211 Geneva 14, Switzerland. ioannis.petropoulos@hcuge.ch
Margetis
Panagiotis I
PI
Antonelou
Marianna H
MH
Koliopoulos
John X
JX
Gartaganis
Sotirios P
SP
Margaritis
Lukas H
LH
Papassideri
Issidora S
IS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003930:Diabetic Retinopathy / Q000097:blood*; D004591:Electrophoresis, Polyacrylamide Gel; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005260:Female; D006021:Glycophorins / Q000378:metabolism; D018056:Hemorheology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D013049:Spectrin / Q000378:metabolism
D001457:Anion Exchange Protein 1, Erythrocyte; D006021:Glycophorins; D008565:Membrane Proteins; C454201:SLC4A1 protein, human; C042732:erythrocyte membrane band 8 protein, human; D013049:Spectrin