Aminoguanidine does not inhibit the initial phase of experimental diabetic retinopathy in rats

H. P. Hammes, S. Syed Ali, M. Uhlmann, A. Weiss, K. Federlin, K. Geisen, M. Brownlee

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

We have previously shown that long-term administration of aminoguanidine, an inhibitor of advanced glycosylation product formation, reduces the extent of experimental diabetic retinopathy in the rat by 85%. In order to determine whether the residual retinopathy that developed despite aminoguanidine was attributable to advanced glycation endproduct formation, a time-course study was performed in three different groups of male Wistar rats: non-diabetic controls (NC), streptozotocin-diabetic controls (DC) and streptozotocin-diabetic rats treated with aminoguanidine HCL, 50 mg/100 ml drinking water (D-AG). Eyes were obtained at 24, 32, 44 and 56 weeks of diabetes/treatment duration and morphologic evaluation was done on retinal digest preparations. At 56 weeks, retinal basement membrane thickness was additionally measured. After 24 weeks of diabetes, the number of acellular capillaries was significantly elevated in DC (44.6±5.7/mm2 of retinal area, NC 19.6±4.9; p<0.001) and increased continuously over time (DC 56 weeks 87.4±15.1; p<0.001 vs DC 24 weeks). In contrast, acellular capillaries in D-AG increased over the first 24 weeks and then remained constant for the rest of the study (D-AG 24 weeks 35.7±5.18; p<0.01 vs NC 24 weeks and NS vs DC 24 weeks; D-AG 56 weeks 42.0±6.20; p NS vs D-AG 24 weeks). Diabetes-associated pericyte loss (DC 24 weeks 2310±170/mm2 of capillary area; NC 24 weeks 3120±190; p<0.001; DC 56 weeks 1570±230; NC 56 weeks 2960±50; p<0.001) was significantly prevented by aminoguanidine after diabetic-like changes over the initial 24 weeks (D-AG 24 weeks 2450±75; p NS vs DC 24 weeks; D-AG 56 weeks 2350±90; p<0.001 vs DC 56 weeks). At 56 weeks, aminoguanidine treatment was associated with a 67.4% reduction in retinal basement membrane thickening. This time-course study demonstrates that aminoguanidine prevents the progression of experimental diabetic retinopathy, and suggests that non AG-inhibitable mechanisms are involved in the initial phase of diabetic retinopathy.

Original languageEnglish (US)
Pages (from-to)269-273
Number of pages5
JournalDiabetologia
Volume38
Issue number3
DOIs
StatePublished - Mar 1995

Fingerprint

Diabetic Retinopathy
Streptozocin
Basement Membrane
Pericytes
Glycosylation
Drinking Water
pimagedine
Wistar Rats

Keywords

  • aminoguanidine
  • Diabetic retinopathy
  • glycation
  • rat model
  • retinal basement membrane

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Hammes, H. P., Syed Ali, S., Uhlmann, M., Weiss, A., Federlin, K., Geisen, K., & Brownlee, M. (1995). Aminoguanidine does not inhibit the initial phase of experimental diabetic retinopathy in rats. Diabetologia, 38(3), 269-273. https://doi.org/10.1007/BF00400629

Aminoguanidine does not inhibit the initial phase of experimental diabetic retinopathy in rats. / Hammes, H. P.; Syed Ali, S.; Uhlmann, M.; Weiss, A.; Federlin, K.; Geisen, K.; Brownlee, M.

In: Diabetologia, Vol. 38, No. 3, 03.1995, p. 269-273.

Research output: Contribution to journalArticle

Hammes, HP, Syed Ali, S, Uhlmann, M, Weiss, A, Federlin, K, Geisen, K & Brownlee, M 1995, 'Aminoguanidine does not inhibit the initial phase of experimental diabetic retinopathy in rats', Diabetologia, vol. 38, no. 3, pp. 269-273. https://doi.org/10.1007/BF00400629
Hammes HP, Syed Ali S, Uhlmann M, Weiss A, Federlin K, Geisen K et al. Aminoguanidine does not inhibit the initial phase of experimental diabetic retinopathy in rats. Diabetologia. 1995 Mar;38(3):269-273. https://doi.org/10.1007/BF00400629
Hammes, H. P. ; Syed Ali, S. ; Uhlmann, M. ; Weiss, A. ; Federlin, K. ; Geisen, K. ; Brownlee, M. / Aminoguanidine does not inhibit the initial phase of experimental diabetic retinopathy in rats. In: Diabetologia. 1995 ; Vol. 38, No. 3. pp. 269-273.
@article{635a18c6033541e2918647fd2eb0a4bc,
title = "Aminoguanidine does not inhibit the initial phase of experimental diabetic retinopathy in rats",
abstract = "We have previously shown that long-term administration of aminoguanidine, an inhibitor of advanced glycosylation product formation, reduces the extent of experimental diabetic retinopathy in the rat by 85{\%}. In order to determine whether the residual retinopathy that developed despite aminoguanidine was attributable to advanced glycation endproduct formation, a time-course study was performed in three different groups of male Wistar rats: non-diabetic controls (NC), streptozotocin-diabetic controls (DC) and streptozotocin-diabetic rats treated with aminoguanidine HCL, 50 mg/100 ml drinking water (D-AG). Eyes were obtained at 24, 32, 44 and 56 weeks of diabetes/treatment duration and morphologic evaluation was done on retinal digest preparations. At 56 weeks, retinal basement membrane thickness was additionally measured. After 24 weeks of diabetes, the number of acellular capillaries was significantly elevated in DC (44.6±5.7/mm2 of retinal area, NC 19.6±4.9; p<0.001) and increased continuously over time (DC 56 weeks 87.4±15.1; p<0.001 vs DC 24 weeks). In contrast, acellular capillaries in D-AG increased over the first 24 weeks and then remained constant for the rest of the study (D-AG 24 weeks 35.7±5.18; p<0.01 vs NC 24 weeks and NS vs DC 24 weeks; D-AG 56 weeks 42.0±6.20; p NS vs D-AG 24 weeks). Diabetes-associated pericyte loss (DC 24 weeks 2310±170/mm2 of capillary area; NC 24 weeks 3120±190; p<0.001; DC 56 weeks 1570±230; NC 56 weeks 2960±50; p<0.001) was significantly prevented by aminoguanidine after diabetic-like changes over the initial 24 weeks (D-AG 24 weeks 2450±75; p NS vs DC 24 weeks; D-AG 56 weeks 2350±90; p<0.001 vs DC 56 weeks). At 56 weeks, aminoguanidine treatment was associated with a 67.4{\%} reduction in retinal basement membrane thickening. This time-course study demonstrates that aminoguanidine prevents the progression of experimental diabetic retinopathy, and suggests that non AG-inhibitable mechanisms are involved in the initial phase of diabetic retinopathy.",
keywords = "aminoguanidine, Diabetic retinopathy, glycation, rat model, retinal basement membrane",
author = "Hammes, {H. P.} and {Syed Ali}, S. and M. Uhlmann and A. Weiss and K. Federlin and K. Geisen and M. Brownlee",
year = "1995",
month = "3",
doi = "10.1007/BF00400629",
language = "English (US)",
volume = "38",
pages = "269--273",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Aminoguanidine does not inhibit the initial phase of experimental diabetic retinopathy in rats

AU - Hammes, H. P.

AU - Syed Ali, S.

AU - Uhlmann, M.

AU - Weiss, A.

AU - Federlin, K.

AU - Geisen, K.

AU - Brownlee, M.

PY - 1995/3

Y1 - 1995/3

N2 - We have previously shown that long-term administration of aminoguanidine, an inhibitor of advanced glycosylation product formation, reduces the extent of experimental diabetic retinopathy in the rat by 85%. In order to determine whether the residual retinopathy that developed despite aminoguanidine was attributable to advanced glycation endproduct formation, a time-course study was performed in three different groups of male Wistar rats: non-diabetic controls (NC), streptozotocin-diabetic controls (DC) and streptozotocin-diabetic rats treated with aminoguanidine HCL, 50 mg/100 ml drinking water (D-AG). Eyes were obtained at 24, 32, 44 and 56 weeks of diabetes/treatment duration and morphologic evaluation was done on retinal digest preparations. At 56 weeks, retinal basement membrane thickness was additionally measured. After 24 weeks of diabetes, the number of acellular capillaries was significantly elevated in DC (44.6±5.7/mm2 of retinal area, NC 19.6±4.9; p<0.001) and increased continuously over time (DC 56 weeks 87.4±15.1; p<0.001 vs DC 24 weeks). In contrast, acellular capillaries in D-AG increased over the first 24 weeks and then remained constant for the rest of the study (D-AG 24 weeks 35.7±5.18; p<0.01 vs NC 24 weeks and NS vs DC 24 weeks; D-AG 56 weeks 42.0±6.20; p NS vs D-AG 24 weeks). Diabetes-associated pericyte loss (DC 24 weeks 2310±170/mm2 of capillary area; NC 24 weeks 3120±190; p<0.001; DC 56 weeks 1570±230; NC 56 weeks 2960±50; p<0.001) was significantly prevented by aminoguanidine after diabetic-like changes over the initial 24 weeks (D-AG 24 weeks 2450±75; p NS vs DC 24 weeks; D-AG 56 weeks 2350±90; p<0.001 vs DC 56 weeks). At 56 weeks, aminoguanidine treatment was associated with a 67.4% reduction in retinal basement membrane thickening. This time-course study demonstrates that aminoguanidine prevents the progression of experimental diabetic retinopathy, and suggests that non AG-inhibitable mechanisms are involved in the initial phase of diabetic retinopathy.

AB - We have previously shown that long-term administration of aminoguanidine, an inhibitor of advanced glycosylation product formation, reduces the extent of experimental diabetic retinopathy in the rat by 85%. In order to determine whether the residual retinopathy that developed despite aminoguanidine was attributable to advanced glycation endproduct formation, a time-course study was performed in three different groups of male Wistar rats: non-diabetic controls (NC), streptozotocin-diabetic controls (DC) and streptozotocin-diabetic rats treated with aminoguanidine HCL, 50 mg/100 ml drinking water (D-AG). Eyes were obtained at 24, 32, 44 and 56 weeks of diabetes/treatment duration and morphologic evaluation was done on retinal digest preparations. At 56 weeks, retinal basement membrane thickness was additionally measured. After 24 weeks of diabetes, the number of acellular capillaries was significantly elevated in DC (44.6±5.7/mm2 of retinal area, NC 19.6±4.9; p<0.001) and increased continuously over time (DC 56 weeks 87.4±15.1; p<0.001 vs DC 24 weeks). In contrast, acellular capillaries in D-AG increased over the first 24 weeks and then remained constant for the rest of the study (D-AG 24 weeks 35.7±5.18; p<0.01 vs NC 24 weeks and NS vs DC 24 weeks; D-AG 56 weeks 42.0±6.20; p NS vs D-AG 24 weeks). Diabetes-associated pericyte loss (DC 24 weeks 2310±170/mm2 of capillary area; NC 24 weeks 3120±190; p<0.001; DC 56 weeks 1570±230; NC 56 weeks 2960±50; p<0.001) was significantly prevented by aminoguanidine after diabetic-like changes over the initial 24 weeks (D-AG 24 weeks 2450±75; p NS vs DC 24 weeks; D-AG 56 weeks 2350±90; p<0.001 vs DC 56 weeks). At 56 weeks, aminoguanidine treatment was associated with a 67.4% reduction in retinal basement membrane thickening. This time-course study demonstrates that aminoguanidine prevents the progression of experimental diabetic retinopathy, and suggests that non AG-inhibitable mechanisms are involved in the initial phase of diabetic retinopathy.

KW - aminoguanidine

KW - Diabetic retinopathy

KW - glycation

KW - rat model

KW - retinal basement membrane

UR - http://www.scopus.com/inward/record.url?scp=0028876818&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028876818&partnerID=8YFLogxK

U2 - 10.1007/BF00400629

DO - 10.1007/BF00400629

M3 - Article

C2 - 7758871

AN - SCOPUS:0028876818

VL - 38

SP - 269

EP - 273

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 3

ER -