Interaction Between Dystrophin Protein 71 (dp71), Inner Blood Retinal Barrier And Dexamethasone

Abstract

Purpose: : To explore the interactions between Dystrophin protein 71 (Dp71), a sub-membranous cytoskeleton protein, and the blood retinal barrier (BRB), and a possible protective effect of dexamethasone through the regulation of Dp71.

Methods: : An improved quantifiable BRB breakdown model in mice was developed and used. In brief, the lenses were pricked with a needle to induce BRB breakdown, and the BRB permeability was quantified at various time-points (24h, 48h, and 72h) after lens surgery in C57BL6/J mice (BRB breakdown group) by the Bleu Evans method. The Dp71 expressions (quantitative RT-PCR analysis of RNA) and protein levels (Western Blot) were also estimated and compare to controls. All these measurements were repeated after intravitreal injection of dexamethasone (first with 4µg and then 10µg). The BRB permeability was also measured in Dp71-null mice.

Results: : BRB permeability in BRB breakdown group was more than 2-fold higher compared to controls 24h after lens surgery. The Dp71 RNA decreased at 24h and its protein level decreased at 72h. Absence of Dp71 (Dp71-null mice) induced also in return a BRB breakdown. The Dp71 RNA and protein levels returned almost to normal after dexamethasone intravitreal injection despite no effect on BRB itself at this dose in this model.

Conclusions: : Interaction does exist between Dp71 and BRB. Indeed, this inner BRB breakdown model leads to a decrease of Dp71. Absence of Dp71 not only induces or maintains the BRB permeability but may also have effect on Muller cells and retinal homeostasis as it has been shown before, which may participate to visual acuity decreases and retinal cells suffering in chronic BRB breakdown. Dexamethasone has a protective effect in this model by restoring the Dp71 mRNA and protein levels.

Keywords: edema • pump/barrier function