This article is part of Ophthalmology Advisor’s Focus on Retina coverage from the 2021 meeting of the American Academy of Ophthalmology, held in New Orleans from November 12 to 15, 2021. The team at Ophthalmology Advisor will be reporting on a variety of the research presented by the retinal experts at the AAO. Check back for more from the AAO 2021 Meeting.
In patients with glaucoma, retinal ganglion cell (RGC) transplantation may potentially restore vision loss. Findings from a study assessing the role of optic nerve injury, proapoptotic signaling, and the internal limiting membrane (ILM) on RGC survival and engraftment were presented at the American Academy of Ophthalmology 2021 meeting, held in New Orleans from November 12-15.
Investigators differentiated human embryonic stem cells into RGCs and either transplanted them onto organotypic retinal explants or injected them intravitreally in immunosuppressed mice. To elucidate the role of the ILM or optic nerve injury, researchers digested the ILM with pronase-E or performed optic nerve crush more than 2 weeks before transplantation. The researchers also knocked out DLK using CRISPR or inhibited DLK signaling using tozasertib.
Consistent with existing literature, investigators found that the survival of the RGCs was 9.2%±3.7% in explants at 1 week, and less than 1% in vivo at 2 weeks. Inhibition of DLK signaling increased graft survival by greater than 50% (P <.01) while enzymatic disruption of the ILM increased structural RGC engraftment by greater than 10-fold (P <.001). Investigators found enhanced survival and structural integration in eyes with previous optic nerve injury in comparison to healthy eyes in vivo.
“Interventions to promote survival and functional engraftment of RGCs into the recipient retina may be required for RGC replacement to restore visual function in human patients with optic neuropathy,” researchers concluded.
Johnson TV, Zhang KY, Welsbie DS, Quigley HA, Zack DJ. Enabling RGC transplantation through modification of donor neuron intrinsic signaling and the recipient microenvironment. Paper Presented at: American Academy of Ophthalmology 2021 Annual Meeting; November 12-15, 2021; New Orleans. Abstract PA042.