Interventions Influence Retinal Ganglion Cell Transplantation Survival

Retina, LM
Retina. Light micrograph (LM) of a section through a retina. The eye works by allowing light to be focused by the lens onto the retina. The retina contains specialised light sensitive photoreceptor cells (top) used to distinguish between colours (cone cells) and to see at night (rod cells). The light is relayed as electrical signals through sensory nerve cells, called bipolar cells ( centre purple cells). The two layers above and below the bipolar nerve cells are synaptic layers, where the dendrites and axons of the photoreceptors and neurons pass on the signals to others below them. The lowest layers are made up of ganglion nerve cells which pass the signals to the brain and the choroid layer that lines the inside of the eye underneath the retina and is pigmented to prevent light reflecting inside the eye distorting the image. Magnification: x120 when printed 10cm wide.
A study says clinicians may need to initiate interventions to promote the survival and functional engraftment of the cells in the recipient.

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. 

Visit Ophthalmology Advisor’s conference section for the complete Focus on Retina coverage from the AAO 2021.

 

Reference 

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.