Chemokines may enhance retinal ganglion cell migration and integration
DEC 28, 2022
Stromal cell–derived factor-1 (SDF1) chemokine shows potential in directing integration of transplanted retinal ganglion cells (RGCs) for the replacement of RGCs lost in chronic optic neuropathies.
The study first identified stromal cell–derived factor-1 (SDF1) as the most potent chemokine for RGC recruitment from 6 possible candidates using a transwell assay, subsequently evaluating for any dose-dependent effect of SDF1 (0, 10, 50, 200, and 500 ng/mL) on cell migration. An in vivo analysis was then performed in which differentiated RGCs from mouse and human stem cells were transplanted subretinally into mice, while SDF1 was injected intravitreally. Mouse retinas were collected after 3 days, and retinal ganglion cell distribution was evaluated using reconstructed, tiled, z-stacked images.
Transretinal migration of RGCs into the ganglion cell layer was noted both spontaneously and in response to SDF1 injection. In the eyes treated with SDF1, there was a 2.7-fold increase in RGC migration, with some of these cells directing axons towards the optic nerve head. No cells were observed migrating into the vitreous, for which the internal limiting membrane is thought to serve as a stopgap. Comparable RGC migration in response to SDF1 treatment was noted in both in vitro and in vivo environments (approximately 40%).
Although many RGC cell bodies were observed colocalizing to the ganglion cell layer, whether they form synaptic connections with neighboring cells has yet to be demonstrated. Moreover, a large portion of RGCs remained subretinal. It will be interesting to see if there is a specific subtype of RGC that is SDF1-responsive and if other chemokines could increase the migration efficiency.
Patients can be informed that significant progress is being made to bring retinal cell replacement therapies to the clinic.