MSCs act as biopatches for blood-retinal barrier preservation to enhance functional recovery after retinal I/R

Retinal ischemia/reperfusion (I/R) is one of the most common pathologies of many vision-threatening diseases and is caused by blood-retinal barrier (BRB) breakdown and the resulting inflammatory infiltration. Targeting BRB is promising for retinal I/R treatment. Mesenchymal stromal cells (MSCs) are emerging as novel therapeutic strategies. Although intravitreal injection targets the retina, the restricted number of injected cells still requires the precise biodistribution of MSCs near the injury site. Here, we found that retinal I/R led to BRB breakdown, which induced protein and cell leakage from the circulation. Retinal cell death and diminished visual function were subsequently detected. Moreover, the expression of the chemokine CCL5 increased after retinal I/R, and CCL5 colocalized with the BRB. We then overexpressed CCR5 in human induced pluripotent stem cell-derived MSCs (iMSCs). In vivo, intravitreal-injected iMSC^CCR5 preferentially migrated and directly integrated into the BRB, which preferably restored BRB integrity and eventually promoted retinal function recovery after retinal I/R. In summary, our work suggested that iMSCs act as biopatches for BRB preservation and that iMSC-based therapy is a promising therapeutic approach for retinal diseases related to I/R.

MT: RNA/DNA Editing; blood-retinal barrier; cell therapy; mesenchymal stromal cells; retinal ischemia/reperfusion.