A Role of Reactive Gliosis in Diabetic Retinopathy

A Role of Reactive Gliosis in Diabetic Retinopathy

Field: Other

Authors: Lundkvist, Andrea
Pekny, Milos

Address of presenting
author: Box 440
405 30 Goteborg

E-mail: Andrea.Lundkvist@medkem.gu.se

Phone: 031-7733472

Fax: 031-416108

Text of abstract: Astrocytes are the most abundant cells in the central nervous system (CNS) but their function remain largely unclear. Many pathological conditions affecting the CNS result in the activation of astrocytes, a phenomenon called reactive gliosis. These situations include CNS injury, diabetic retinopathy (DR), CNS ischemia, reaction to a growing tumor and neurodegenerative disease. Upregulation of intermediate filaments (IFs), a component of the cytoskeleton, is a hallmark of astrocyte activation. To study the role of RG in different pathological situations affecting the CNS, we have generated mice deficient for GFAP and vimentin, two IF proteins expressed in astroglial cells and highly overexpressed in reactive astrocytes. We have found that reactive astrocytes of these mice cannot form Ifs and that Ifs are required for normal formation of glial scar following brain or spinal cord trauma.
Using a model of STZ-induced diabetes in rats, it was found that upregulation of Ifs in astrocytes in the retina is present long before any vascular or neuronal damage can be detected. Thus, an intriguing possibility exists that such RG may represent an important step in the pathogenesis of DR and could therefore be the target in diabetic patients as part of the prevention or therapy of DR. Following a chemical induction of diabetes, our transgenic models enable to evaluate the role of astrocytic Ifs in the development of DR. Various aspects of astrocyte function such as maintenance of blood-brain barrier can also be addressed.
The second part of the project will focus at the identification of differentially expressed genes in RG using the DNA microarray approach. This may lead to the identification of molecules and biochemical pathways connected with RG.

Keywords: astrocytes, intermediate filaments, reactive gliosis, transgenic mice, diabetic retinopathy

	A Role of Reactive Gliosis in Diabetic Retinopathy
Field:	Other
Authors:	Lundkvist, Andrea Pekny, Milos
Address of presenting author:	Box 440 405 30 Goteborg
E-mail:	Andrea.Lundkvist@medkem.gu.se
Phone:	031-7733472
Fax:	031-416108
Text of abstract:	Astrocytes are the most abundant cells in the central nervous system (CNS) but their function remain largely unclear. Many pathological conditions affecting the CNS result in the activation of astrocytes, a phenomenon called reactive gliosis. These situations include CNS injury, diabetic retinopathy (DR), CNS ischemia, reaction to a growing tumor and neurodegenerative disease. Upregulation of intermediate filaments (IFs), a component of the cytoskeleton, is a hallmark of astrocyte activation. To study the role of RG in different pathological situations affecting the CNS, we have generated mice deficient for GFAP and vimentin, two IF proteins expressed in astroglial cells and highly overexpressed in reactive astrocytes. We have found that reactive astrocytes of these mice cannot form Ifs and that Ifs are required for normal formation of glial scar following brain or spinal cord trauma. Using a model of STZ-induced diabetes in rats, it was found that upregulation of Ifs in astrocytes in the retina is present long before any vascular or neuronal damage can be detected. Thus, an intriguing possibility exists that such RG may represent an important step in the pathogenesis of DR and could therefore be the target in diabetic patients as part of the prevention or therapy of DR. Following a chemical induction of diabetes, our transgenic models enable to evaluate the role of astrocytic Ifs in the development of DR. Various aspects of astrocyte function such as maintenance of blood-brain barrier can also be addressed. The second part of the project will focus at the identification of differentially expressed genes in RG using the DNA microarray approach. This may lead to the identification of molecules and biochemical pathways connected with RG.

Keywords:	astrocytes, intermediate filaments, reactive gliosis, transgenic mice, diabetic retinopathy

Index

Created 2000-03-15

Department of Physiological Sciences, Lund University

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