Abstract
Plasminogen activator inhibitor-1 is secreted bidirectionally by endothelial cells, acts as the primary regulator of fibrinolysis and as a key modulator of extracellular matrix proteolysis. Elevated farum levels of plasminogen activator inhibitor-1 are observed in serum of diabetic individuals. We investigated whether plasminogen activator inhibitor-1 is overexpressed in capillaries of diabetic donors with nonproliferative retinopathy compared to non-diabetic donors. We also assessed plasminogen activator inhibitor-1 expression in an animal model of retinopathy induced by exposing rabbit retinas to insulin-like growth factor-I. Colloidal gold immunocytochemistry was used to quantify plasminogen activator-1 antigen in donor retinas from diabetic subjects (n = 10) and control subjects (n = 10). This technique was also used to examine expression of plasminogen activator inhibitor-1 for correlation with retinal changes in the insulin-like growth factor-I-induced retinopathy model (n = 14). Plasminogen activator inhibitor-1 immunoreactivity was significantly increased in the retinas of all diabetic subjects as compared to controls. In the rabbit model, the expression of plasminogen activator inhibitor-1 immunoreactivity correlated with pathological retinal changes. In both the diabetic human and insulin-like growth factor-1-injected rabbit, overproduction of plasminogen activator inhibitor-1 was seen within the lumen of capillaries, within the cytoplasm of endothelial cells and in the basement membrane and extracellular matrix surrounding these capillaries. Minimal plasminogen activator inhibitor-1 was detected in the retinas of non-diabetics and in control rabbits injected with either heat-inactivated insulin-like growth factor-I or balanced salt solution. These studies support the conclusion that plasminogen activator inhibitor-1 is overexpressed in the retinal capillaries of diabetics with nonproliferative diabetic retinopathy and in rabbits with insulin-like growth factor-I-induced retinopathy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 233-244 |
| Number of pages | 12 |
| Journal | Experimental Eye Research |
| Volume | 63 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1996 |
| Externally published | Yes |
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Keywords
- diabetic retinopathy
- immunocytochemistry
- insulin-like growth factor-I
- plasminogen activator inhibitor
- retinal endothelial cells
ASJC Scopus subject areas
- Ophthalmology
- Sensory Systems
Cite this
Plasminogen activator inhibitor-1 overexpression in nonproliferative diabetic retinopathy. / Grant, Maria B.; Ellis, E. Ann; Caballero, Sergio; Mames, Robert N.
In: Experimental Eye Research, Vol. 63, No. 3, 09.1996, p. 233-244.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Plasminogen activator inhibitor-1 overexpression in nonproliferative diabetic retinopathy
AU - Grant, Maria B.
AU - Ellis, E. Ann
AU - Caballero, Sergio
AU - Mames, Robert N.
PY - 1996/9
Y1 - 1996/9
N2 - Plasminogen activator inhibitor-1 is secreted bidirectionally by endothelial cells, acts as the primary regulator of fibrinolysis and as a key modulator of extracellular matrix proteolysis. Elevated farum levels of plasminogen activator inhibitor-1 are observed in serum of diabetic individuals. We investigated whether plasminogen activator inhibitor-1 is overexpressed in capillaries of diabetic donors with nonproliferative retinopathy compared to non-diabetic donors. We also assessed plasminogen activator inhibitor-1 expression in an animal model of retinopathy induced by exposing rabbit retinas to insulin-like growth factor-I. Colloidal gold immunocytochemistry was used to quantify plasminogen activator-1 antigen in donor retinas from diabetic subjects (n = 10) and control subjects (n = 10). This technique was also used to examine expression of plasminogen activator inhibitor-1 for correlation with retinal changes in the insulin-like growth factor-I-induced retinopathy model (n = 14). Plasminogen activator inhibitor-1 immunoreactivity was significantly increased in the retinas of all diabetic subjects as compared to controls. In the rabbit model, the expression of plasminogen activator inhibitor-1 immunoreactivity correlated with pathological retinal changes. In both the diabetic human and insulin-like growth factor-1-injected rabbit, overproduction of plasminogen activator inhibitor-1 was seen within the lumen of capillaries, within the cytoplasm of endothelial cells and in the basement membrane and extracellular matrix surrounding these capillaries. Minimal plasminogen activator inhibitor-1 was detected in the retinas of non-diabetics and in control rabbits injected with either heat-inactivated insulin-like growth factor-I or balanced salt solution. These studies support the conclusion that plasminogen activator inhibitor-1 is overexpressed in the retinal capillaries of diabetics with nonproliferative diabetic retinopathy and in rabbits with insulin-like growth factor-I-induced retinopathy.
AB - Plasminogen activator inhibitor-1 is secreted bidirectionally by endothelial cells, acts as the primary regulator of fibrinolysis and as a key modulator of extracellular matrix proteolysis. Elevated farum levels of plasminogen activator inhibitor-1 are observed in serum of diabetic individuals. We investigated whether plasminogen activator inhibitor-1 is overexpressed in capillaries of diabetic donors with nonproliferative retinopathy compared to non-diabetic donors. We also assessed plasminogen activator inhibitor-1 expression in an animal model of retinopathy induced by exposing rabbit retinas to insulin-like growth factor-I. Colloidal gold immunocytochemistry was used to quantify plasminogen activator-1 antigen in donor retinas from diabetic subjects (n = 10) and control subjects (n = 10). This technique was also used to examine expression of plasminogen activator inhibitor-1 for correlation with retinal changes in the insulin-like growth factor-I-induced retinopathy model (n = 14). Plasminogen activator inhibitor-1 immunoreactivity was significantly increased in the retinas of all diabetic subjects as compared to controls. In the rabbit model, the expression of plasminogen activator inhibitor-1 immunoreactivity correlated with pathological retinal changes. In both the diabetic human and insulin-like growth factor-1-injected rabbit, overproduction of plasminogen activator inhibitor-1 was seen within the lumen of capillaries, within the cytoplasm of endothelial cells and in the basement membrane and extracellular matrix surrounding these capillaries. Minimal plasminogen activator inhibitor-1 was detected in the retinas of non-diabetics and in control rabbits injected with either heat-inactivated insulin-like growth factor-I or balanced salt solution. These studies support the conclusion that plasminogen activator inhibitor-1 is overexpressed in the retinal capillaries of diabetics with nonproliferative diabetic retinopathy and in rabbits with insulin-like growth factor-I-induced retinopathy.
KW - diabetic retinopathy
KW - immunocytochemistry
KW - insulin-like growth factor-I
KW - plasminogen activator inhibitor
KW - retinal endothelial cells
UR - http://www.scopus.com/inward/record.url?scp=0030248421&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030248421&partnerID=8YFLogxK
U2 - 10.1006/exer.1996.0112
DO - 10.1006/exer.1996.0112
M3 - Article
C2 - 8943696
AN - SCOPUS:0030248421
VL - 63
SP - 233
EP - 244
JO - Experimental Eye Research
JF - Experimental Eye Research
SN - 0014-4835
IS - 3
ER -