Purpose
The RPE barrier is the gatekeeper of the choroidal circulation which is responsible for ~80% of blood supplies in the eye. To investigate the mechanism and significance of RPE barrier breakdown in diabetic retinopathy (DR), we recently developed a semi-quantitative assay for measuring RPE barrier leakage (IOVS, 52:2160). To take one step further and to determine the significance of RPE barrier-specific leakage in DR and other retinal diseases, we examined the dynamics of macromolecules passed through the RPE barrier in diabetic rodents.
Methods
Diabetes was induced in rodents by streptozotocin (STZ). RPE barrier-specific leakage was measured de novo by florescent microscopy of retinal sections from diabetic rodents injected with florescent dextran intravenously (IOVS, 52:2160). Computer-assisted quantification was used to determine the relative levels of RPE or endothelial barrier-specific leakage.
Results
The RPE barrier-specific leakage was observed immediately after intravenous injection of florescent dextran, indicating that the choroidal circulation was more efficient than the retinal vasculature in delivering blood-content to the retina. While the RPE barrier-specific leakage occurred everywhere, the rate of transporting the leaked material through severe leakage sites was faster (see attached image). In addition, the fluorescent intensity representing RPE barrier-specific leakage appeared to be comparable, if not more, to that from the endothelial barrier.
Conclusions
Since choroidal circulation delivers ~80% of the blood supplies to the eye with a much higher blood flow than that of retinal vasculature, our data clearly suggest a much more prominent role for the RPE barrier in overall blood-retina barrier breakdown in DR. Our data may also provide the cellular mechanism for a significant portion of diabetic macular edema patients who demonstrate the cellular lesion near the RPE by optical coherence tomography imaging.