Dr. Goldberg noted that results from previous research in animal models demonstrated that RGC cells delivered into the vitreous migrated to and integrated into the retina and then grew lengthy axons projecting down the optic nerve and extending to the brain.
However, a low rate of RGC differentiation from progenitor or stem cells in vitro limited further development of RGC cell therapy.
"The signaling pathways that make photoreceptors out of stem cells or retinal progenitor cells have been understood for a long time, but it has been more challenging to define the pathway for specifying RGC fate," Dr. Goldberg said.
To solve this problem, Dr. Goldberg and colleagues undertook a screen of developmentally expressed transcription factors.
In their work, they discovered that a molecular pathway involving Sox4/Sox11 was required for RGC differentiation and optic nerve formation in mice in vivo and was sufficient for promoting differentiation of human induced pluripotent cells and human embryonic stem cells into RGC-like cells in culture [Chang KC et al. J Neurosci. 2017;37:4967-4981].
"The induced cells are structurally and functionally similar to endogenous RGCs," Dr. Goldberg said. "Not only do they look like RGCs and express protein markers typically expressed by the RGCs, but they also mimic RGCs in terms of electrophysiologic activity."
Research developing new biomarkers as study endpoints is also progressing and is important and exciting because of its implications for facilitating the process of candidate discovery and decreasing the time needed to demonstrate efficacy.
Jeffrey L. Goldberg, MD, PhD
E: [email protected]
This article was adapted from Dr. Goldberg's presentation during Glaucoma Subspecialty Day at the 2017 meeting of the American Academy of Ophthalmology. Dr. Goldberg has no financial interests in the products discussed.