The Retinal Ganglion Cell Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration Consortium

Abstract

Purpose: The Retinal Ganglion Cell (RGC) Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) consortium was founded in 2021 to help address the numerous scientific and clinical obstacles that impede development of vision-restorative treatments for patients with optic neuropathies. The goals of the RReSTORe consortium are: (1) to define and prioritize the most critical challenges and questions related to RGC regeneration; (2) to brainstorm innovative tools and experimental approaches to meet these challenges; and (3) to foster opportunities for collaborative scientific research among diverse investigators.

Design and participants: The RReSTORe consortium currently includes > 220 members spanning all career stages worldwide and is directed by an organizing committee comprised of 15 leading scientists and physician-scientists of diverse backgrounds.

Methods: Herein, we describe the structure and organization of the RReSTORe consortium, its activities to date, and the perceived impact that the consortium has had on the field based on a survey of participants.

Results: In addition to helping propel the field of regenerative medicine as applied to optic neuropathies, the RReSTORe consortium serves as a framework for developing large collaborative groups aimed at tackling audacious goals that may be expanded beyond ophthalmology and vision science.

Conclusions: The development of innovative interventions capable of restoring vision for patients suffering from optic neuropathy would be transformative for the ophthalmology field, and may set the stage for functional restoration in other central nervous system disorders. By coordinating large-scale, international collaborations among scientists with diverse and complementary expertise, we are confident that the RReSTORe consortium will help to accelerate the field toward clinical translation.

Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Collaborative science; Neuroregeneration; Optic neuropathy; Regenerative medicine; Vision restoration.

Figure 1

Subtopic discussion subgroups. The Retinal Ganglion Cell Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) consortium is conceptually divided into 5 subtopic discussion subgroups (SDGs). Examples of topics pertinent to each SDG are provided. IPL = inner plexiform layer; RGC = retinal ganglion cell.

Figure 2

Workflow for phase I: consensus-based identification of key topics for discussion. Tasks performed by the organizing committee (blue) and the membership (red) are described, along with relevant timelines. RReSTORe = Retinal Ganglion Cell Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration; SDG = subtopic discussion subgroup.

Figure 3

Enthusiasm scores for proposed discussion topics in phase I. After curation and summary of all submitted discussion topics submitted by Retinal Ganglion Cell Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) members (see Appendix S2 for full descriptions and subtopics), members reviewed the proposed topics and submitted enthusiasm scores, based on a 10-point Likert Scale where 1 represented no enthusiasm and 10 represented highest possible enthusiasm. A, Topics for subtopic discussion group (SDG) #1: Retinal Ganglion Cell (RGC) Development and Differentiation. B, Topics for SDG #2: Transplantation Methods and Models. C, Topics for SDG #3: RGC Survival, Maturation, and Host Interactions. D, Topics for SDG #4: Inner Retinal Wiring. E, Topics for SDG #5: Eye-to-Brain Connectivity. Violin plots of enthusiasm scores are shown. Dashed lines, median. Dotted lines, interquartile range. ILM = internal limiting membrane; IPL = inner plexiform layer.

Figure 4

Age and subtopic discussion group (SDG) membership of survey respondents. A, To maintain anonymity, age was binned by 5 or 10 years. B, Refer to Figure 1 for SDG names and example topics.

Figure 5

Results from 1-year impact survey. Respondents were asked to rate their level of agreement with the indicated statements (A-J) on a 5-point Likert scale, with 1 representing “strongly disagree” and 5 representing “strong agree.” Refer to Appendix S4 for survey questions. RGC = retinal ganglion cell; RReSTORe = Retinal Ganglion Cell Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration.