Enhanced expression of intracellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroid
D S McLeod1, D J Lefer, C Merges
1Wilmer Ophthalmologic Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Insights
Diabetic retinopathy involves increased intercellular adhesion molecule-1 (ICAM-1) and P-selectin in the choroid and retina. This may enhance leukocyte adhesion, contributing to microvascular damage in diabetes.
Area of Science:
- Ophthalmology
- Immunology
- Diabetic Complications
Background:
- Leukocyte adhesion to vascular endothelium is critical in disease.
- Intercellular adhesion molecule-1 (ICAM-1), E-selectin, and P-selectin are key adhesion molecules.
- Their role in diabetic retinopathy requires further investigation.
Purpose of the Study:
- To investigate the immunolocalization of ICAM-1, E-selectin, and P-selectin in human postmortem retinal and choroidal tissue.
- To compare expression levels between non-diabetic and diabetic subjects.
Main Methods:
- Immunohistochemical analysis of postmortem human retinal and choroidal sections.
- Quantification of ICAM-1, E-selectin, and P-selectin expression.
- Assessment of neutrophil infiltration.
Main Results:
- ICAM-1 was significantly elevated in diabetic choroidal and retinal vasculature.
- P-selectin was upregulated in diabetic choroidal arteries and veins.
- Neutrophil numbers were significantly increased in diabetic choroid and retina.
Conclusions:
- ICAM-1 and P-selectin are upregulated in the choroidal vasculature of diabetic subjects.
- ICAM-1 is also upregulated in the diabetic retina.
- Increased expression of these adhesion molecules may promote leukocyte adhesion and microvascular injury in diabetic eyes.
Abstract:
Elevated expression of intercellular adhesion molecule-1 (ICAM-1) as well as E- and P-selectin occurs on the vascular endothelium in a number of disease states and is thought to play an early critical role in the adhesion of circulating leukocytes to the endothelium. The goal of the present study was to investigate the immunolocalization of these molecules in the retina and choroid of postmortem human tissue sections from nondiabetic and diabetic subjects. Whereas ICAM-1 was localized primarily within the choriocapillaris of nondiabetic subjects, immunoreactivity in diabetics was significantly elevated throughout the choroidal vasculature and within retinal blood vessels (P < 0.05). In the choroid, P-selectin was most prominent in veins of the nondiabetic, whereas in diabetics, P-selectin was significantly elevated in arteries (P < 0.001) and veins (P < 0.05) and, in some cases, was also observed in choriocapillaris. P-selectin immunoreactivity was not observed in the retina of any subject. E-selectin immunoreactivity was not observed in choroid or retina in any subjects. Neutrophil numbers per square millimeter of tissue were significantly elevated in diabetic choroid (P < 0.05) and retina (P < 0.001). Our results demonstrate that ICAM-1 and P-selectin are constitutively expressed in the normal choroid and are upregulated in the choroidal vasculature in diabetes, but only ICAM-1 was upregulated in the retina of diabetic subjects. Increased cell adhesion molecule expression may contribute to the retinal and choroidal microangiopathy observed in diabetics by enhancing leukocyte adhesion and consequently the incidence of capillary obstruction and endothelial cell injury.
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