HORMONES &NEOVASCULARIZATION IN DIABETIC RETINOPATHY

  • Grant, Maria, (PI)
  • Abcouwer, Steven (PI)
  • Mohr, Susanne (PI)

Project: Research project

Description

Proliferative retinopathy is one of the most common and serious vascular
complications of diabetes. The major pathological finding in the eye
results form proliferation of retinal capillary endothelial cells, causing
new and aberrant capillary growth on the surface of the retina. It is
thought that growth hormone may be one of several important causes of this
condition. However, many actions previously attributed to growth hormone
are now known to be mediated by insulin-like growth factors (IFG). I will
concentrate on determining the role of insulin-like growth factor I in the
development of retinal neovascularization, with emphasis on its
interactions with other angiogenic agents. I will use in vitro methods to study three key aspects of
neovascularization: 1) production by the endothelial cell of enzymes which
cause proteolysis of the extracellular matrix, 2) migration of the
endothelial cell, and 3) proliferation of the endothelial cell. Human
endothelial cell cultures derived from both diabetic retinas and non-
diabetic retinas will be used. The use of diabetic endothelial cell
cultures will enable me to also test whether an inherent defect exists in
the diabetic endothelial cell. Both diabetic and non-diabetic cells will be studied under conditions of
altered pH, varying glucose and insulin concentrations. These cell
cultures will be compared with regard to ultrastructure, growth capacity
and ability to release proteases. IGF I will be characterized along with
established angiogenic factors on growth, movement, and enzyme production
by these cells. I will test whether IGF I can induce the endothelial cells
to invade a three-dimensional collagen matrix and form a network of
capillary-like tubular structures. Also, the degradative potential of
growth factor stimulated endothelial cells will be investigated using
radiolabeled extracellular matrices. An in vivo model for studying angiogenesis has also been developed. When
Elvax 4 pellets are placed in the cornea of rabbit eyes, IGF I induces
vessels from the limbus to grow toward the pellet and surround it. The
protocols of this proposal provide for the experimental dissection of the
biochemical steps involved in neovascularization. A better understanding
of how these phenomena are regulated at the cellular level could allow for
the identification of specific inhibitors of neovascularization.
StatusFinished
Effective start/end date8/1/898/31/16

Funding

  • National Institutes of Health: $452,377.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $356,482.00
  • National Institutes of Health: $519,583.00
  • National Institutes of Health: $327,375.00
  • National Institutes of Health: $517,609.00
  • National Institutes of Health: $216,812.00
  • National Institutes of Health
  • National Institutes of Health: $352,659.00
  • National Institutes of Health: $212,426.00
  • National Institutes of Health: $364,237.00
  • National Institutes of Health: $167,028.00
  • National Institutes of Health: $452,378.00
  • National Institutes of Health: $212,152.00
  • National Institutes of Health
  • National Institutes of Health: $326,813.00
  • National Institutes of Health: $71,410.00
  • National Institutes of Health: $319,682.00
  • National Institutes of Health: $360,112.00
  • National Institutes of Health: $114,813.00
  • National Institutes of Health
  • National Institutes of Health: $341,648.00
  • National Institutes of Health: $326,250.00
  • National Institutes of Health

Fingerprint

Diabetic Retinopathy
Endothelial Cells
Insulin-Like Growth Factor I
Retina
Extracellular Matrix
Plasminogen Activator Inhibitor 1
Somatomedins
Growth
Hormones
Monocytes
Retinal Neovascularization
Bone Marrow
Insulin-Like Growth Factor Binding Protein 3
Cell Communication
Integrins
IGF Type 1 Receptor
Peptide Hydrolases
Basement Membrane
Proteolysis
Angiogenesis Inhibitors

Keywords

  • Medicine(all)