BLOOD-RETINAL BARRIER CHANGES IN RETINOPATHY

Project: Research project

Description

This project proposes to investigate blood-retinal barrier changes in the
retinal pigment epithelium (RPE), Bruch's membrane and the choroid in Royal
College of Surgeons (RCS) dystrophic rats, spontaneously diabetic
Bio-Breeding (BB) rats, and donor eyes from diabetic humans. Intracellular
transport of large molecular weight substances by dystrophic and diabetic
cells will be compared to that in normal RPE cells. RCS and BB rats at
different ages will be injected intravenously with cationic or anionic
isoenzymes of horseradish peroxidase and uptake and intracellular routes of
the tracer will be analyzed with the electron microscope. Possible changes
in permeability through Bruch's membrane and the choriocapillaris during
retinopathy in BB and RCS rats will be studied using the neutral protein,
hemoglobin, as an electron microscope tracer. The luminal surface of the
choriocapillaris endothelium will be studied in BB and RCS rats using
cationic and native ferritin electron microscope techniques in order to
determine the role of differentially distributed luminal surface anionic
sites in the modulation of transendothelial permeability in the normal eye
and during retinopathy. Freeze-fracture, filipin binding and cholera toxin
binding techniques will be used to study possible alterations in the
distribution of membrane cholesterol and gycolipids which could contribute
to a defect in plasma membrane permeability in the RPE of BB rats and
diabetic humans. Rapid freeze, deep etch electron microscope techniques
will be used to study RPE-Bruch's membrane attachments in diabetic humans
and BB rats. The long-term objectives of this research are to determine
the basic mechanisms of blood-retinal barrier changes and the relationship
of such changes to retinopathy. It is anticipated that such data will
contribute to the prevention of and/or treatment of blood-retinal barrier
pathology.
StatusFinished
Effective start/end date12/1/8212/31/11

Funding

  • National Institutes of Health: $346,600.00
  • National Institutes of Health: $222,662.00
  • National Institutes of Health
  • National Institutes of Health: $159,220.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $349,706.00
  • National Institutes of Health: $356,235.00
  • National Institutes of Health: $251,125.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $250,048.00
  • National Institutes of Health
  • National Institutes of Health: $356,843.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $353,275.00
  • National Institutes of Health
  • National Institutes of Health: $216,175.00
  • National Institutes of Health: $251,125.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $173,118.00
  • National Institutes of Health: $251,125.00

Fingerprint

Blood-Retinal Barrier
Permeability
Vascular Endothelial Growth Factor A
Inbred BB Rats
Bruch Membrane
Electrons
Neuroglia
beta Catenin
Endothelial Cells
Retinal Pigments
Diabetic Retinopathy
Phosphatidylinositol 3-Kinase
Transforming Growth Factor beta
Cell Death
Filipin
Choroid
Nitric Oxide
Horseradish Peroxidase
Cholera
Glucose

ASJC

  • Medicine(all)