Related Experiment Video
Updated: Aug 23, 2026
Retinal Pathophysiological Evaluation in a Rat Model
Published on: May 6, 2022
Dynamic contrast-enhanced MRI measurements of passive permeability through blood retinal barrier in diabetic rats
Bruce A Berkowitz1, Robin Roberts, Hongmei Luan
1Department of Anatomy and Cell Biology, and Kresge Eye Institute, Wayne State University, Detroit, Michigan 48201, USA. baberko@med.wayne.edu
Purpose:
To test the hypothesis that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides a useful in vivo measure of passive blood retinal barrier permeability surface area product (BRB PS) in experimental diabetic retinopathy.
Methods:
BRB PS (cm(3)/min) was measured using DCE-MRI and Gd-DTPA (MW 590 Da) in urethane-anesthetized control rats, sodium iodate-treated rats, rats receiving intravitreally injected human serum albumin (HSA) or vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), or in rats that were diabetic for 2, 4, 6, or 8 months.
Results:
Sodium iodate-treated rats exhibited an eightfold increase (P < 0.05) in BRB PS compared to that in control animals. Furthermore, in iodate-treated rats, the average vitreous signal enhancement was linearly dependent on Gd-DTPA dose (r = 0.91, P < 0.0001). Six hours postinjection, VEGF/VPF-treated rats exhibited a threefold increase in BRB PS (P < 0.05) compared to eyes injected with HSA. In 2-, 4-, and 6-month diabetic rats, BRB PS was not significantly different (P > 0.05) from control BRB PS values. After 8 months of diabetes, a twofold increase (P < 0.05) in PS over control PS values was found. DCE-MRI demonstrated that the BRB becomes leaky immediately before death, possibly causing an artificial increase in retinal permeability in methods that require enucleation or retinal isolation to assess permeability.
Conclusions:
DCE-MRI provides a sensitive, noninvasive, and linear assay that accurately measures, without potential artifacts associated with death and enucleation, passive BRB PS in experimental diabetes. DCE-MRI BRB PS measurements are expected to provide a useful surrogate marker of drug treatment efficacy.
Insights
Dynamic contrast-enhanced MRI (DCE-MRI) accurately measures blood retinal barrier permeability (BRB PS) in experimental diabetes. This noninvasive method avoids artifacts, offering a sensitive tool for assessing BRB PS and potential drug efficacy.
Area of Science:
- Ophthalmology
- Medical Imaging
- Physiology
Background:
- Diabetic retinopathy is a leading cause of vision loss.
- Assessing blood retinal barrier (BRB) permeability is crucial for understanding and treating diabetic retinopathy.
- Current methods for measuring BRB permeability may involve artifacts due to animal death or tissue isolation.
Purpose of the Study:
- To evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as an in vivo method for measuring passive blood retinal barrier permeability surface area product (BRB PS).
- To test the hypothesis that DCE-MRI can accurately quantify BRB PS in experimental models of diabetic retinopathy.
Main Methods:
- BRB PS was measured using DCE-MRI with Gd-DTPA in control rats and rats with experimentally induced diabetic retinopathy or vascular endothelial growth factor (VEGF/VPF) induced leakage.
- Measurements were taken in rats at various time points of diabetes (2, 4, 6, 8 months) and after specific treatments.
Main Results:
- Sodium iodate-induced retinopathy showed an eightfold increase in BRB PS.
- VEGF/VPF treatment led to a threefold increase in BRB PS compared to human serum albumin (HSA) controls.
- Significant increases in BRB PS were observed after 8 months of diabetes, but not at earlier time points.
- DCE-MRI indicated BRB leakage occurs just before death, highlighting potential artifacts in other methods.
Conclusions:
- DCE-MRI offers a sensitive, noninvasive, and linear assay for measuring passive BRB PS in experimental diabetes.
- This technique accurately quantifies BRB PS without the artifacts associated with enucleation or animal death.
- DCE-MRI BRB PS measurements are proposed as a valuable surrogate marker for evaluating the efficacy of therapeutic interventions in diabetic retinopathy.
