Intravitreal Delivery of Mesenchymal Stem Cells Loaded onto Hydrogel Affects the Regulatory Expression of Endogenous NGF and BDNF in Ischemic Rat Retina

The utility of a biodegradable hyaluronic acid (HyA)-based hydrogel as a tissue scaffold for intravitreal carriage of mesenchymal stem cells (MSCs) into the retina was tested. A rat model of retinal ischemia-reperfusion (IR) injury was used. DiI-labeled MSCs from three passages were loaded onto hydrogel and injected into the vitreous body of experimental and control eyeballs 1 week after IR. The neutral hydrogel was also modified to a basic pH. A control carrier, 0.01 M phosphate-buffered saline (pH 7.2; PBS) was compared. Retinal tissues were prepared 1 week and 2 weeks after MSCs application. MSCs localization and effects were evaluated on immunostained retinal preparations with confocal microscopy. MSCs localization was apparent in the retinas loaded onto hydrogels, adhering tightly to the inner limiting membrane, whereas those in PBS floated in the vitreous body. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were expressed in the end feet of M$\ddot{u}$ller cells in the normal retina. NGF expression was slightly reduced 2 weeks IR, had expanded into the proximal processes 3 weeks IR, but it appeared reversely 1 week and 2 weeks after MSCs application, respectively. BDNF expression was higher in the ischemic and MSCs-treated ischemic retinas than in the normal and MSCs-treated control retinas, respectively. These findings demonstrate that HyA-based hydrogel is an efficient vehicle for intravitreal MSC transplantation into the retina, and that MSCs thus transplanted induce M$\ddot{u}$ller glial cells to produce growth factors concerned with the survival of retinal ganglion cells.