Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium

Jonathan R Soucy; Erika A Aguzzi; Julie Cho; Michael James Gilhooley; Casey Keuthan; Ziming Luo; Aboozar Monavarfeshani; Meher A Saleem; Xue-Wei Wang; Juilette Wohlschlegel; RReSTORe Consortium; Petr Baranov; Adriana Di Polo; Brad Fortune; Kimberly K Gokoffski; Jeffrey L Goldberg; William Guido; Alex L Kolodkin; Carol A Mason; Yvonne Ou; Thomas A Reh; Ahmara G Ross; Brian C Samuels; Derek Welsbie; Donald J Zack; Thomas V Johnson

doi:10.1186/s13024-023-00655-y

Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium

Mol Neurodegener. 2023 Sep 21;18(1):64. doi: 10.1186/s13024-023-00655-y.

Authors

Jonathan R Soucy¹, Erika A Aguzzi^#², Julie Cho^#³, Michael James Gilhooley^#^{2

4}, Casey Keuthan^#⁵, Ziming Luo^#³, Aboozar Monavarfeshani^#^{6

7}, Meher A Saleem^#⁸, Xue-Wei Wang^#⁹, Juilette Wohlschlegel^#¹⁰; RReSTORe Consortium; Petr Baranov¹, Adriana Di Polo^{11

12}, Brad Fortune¹³, Kimberly K Gokoffski¹⁴, Jeffrey L Goldberg³, William Guido¹⁵, Alex L Kolodkin¹⁶, Carol A Mason¹⁷, Yvonne Ou¹⁸, Thomas A Reh¹⁰, Ahmara G Ross¹⁹, Brian C Samuels²⁰, Derek Welsbie²¹, Donald J Zack^{22

23}, Thomas V Johnson^{24

25}

Collaborators

RReSTORe Consortium:
Abdelrahman Y Fouda, Ajay Ashok, Ala Moshiri, Alain Chedotal, Amberlynn A Reed, Amjad Askary, An-Jey A Su, Anna La Torre, Archana Jalligampala, Ariadna Silva-Lepe, Arupratan Das, Barbara Wirostko, Benjamin J Frankfort, Benjamin Sivyer, Bhagwat Alapure, Brent Young, Brian Clark, Bryan William Jones, Chase Hellmer, Claire Mitchell, Claire Ufongene, Dan Goldman, David Feldheim, David H Gutmann, David J Calkins, David Krizaj, David M Gamm, Diana C Lozano, Diane E Bovenkamp, Dong Feng Chen, Elena Vecino Cordero, Ephraim F Trakhtenberg, Feng Tian, Fengquan Zhou, Gillian J McLellan, Harry A Quigley, Hashem Abu Serhan, James R Tribble, Jason Meyer, Jeff Gross, Jeff S Mumm, Jeremy M Sivak, Jingliang Simon Zhang, Jiun L Do, Jonathan Crowston, Julie Chen, Juliette McGregor, Kalyan C Vinnakota, Kang-Chieh Huang, Karen Peynshaert, Katherine E Uyhazi, Keith Martin, Ken Muller, Kevin K Park, Kin-Sang Cho, Kun-Che Chang, Larry Benowitz, Leonard A Levin, Levi Todd, Lies De Groef, Lieve Moons, Luis Alarcon-Martinez, Mandeep S Singh, Manuel Vidal-Sanz, Mariana S Silveira, Marina Pavlou, Matthew B Veldman, Matthew Van Hook, Melanie Samuel, Mengming Hu, Micalla Peng, Michael Young, Michel Cayouette, Mohammad H Geranmayeh, Mollie Woodworth, Monica Vetter, Nicholas R Marsh-Armstrong, Pete A Williams, Pratheepa Kumari Rasiah, Preeti Subramanian, Qi N Cui, Rebecca M Sappington, Reem Amine, Richard Eva, Robert J Johnston Jr, Roman J Giger, Ross Ethier, Sadaf Abed, Sehrish Nizar Ali Momin, Seth Blackshaw, Shane A Liddelow, Stella Mary, Stephen Atolagbe, Supraja Varadarajan, Tareq I Nabhan, Tasneem Khatib, Tasneem Putliwala Sharma, Thomas Brunner, Tom Greenwell, Tonia S Rex, Trent Watkins, Tudor C Badea, V Vrathasha, Venkata Ramana Murthy Chavali, Viviane M Oliveira-Valença, Wai Lydia Tai, Wyndham M Batchelor, Xian-Jie Yang, Yong Park, Yuan Pan

Affiliations

¹ Department of Ophthalmology, Schepens Eye Research Institute of Mass. Eye and Ear, Harvard Medical School, Boston, MA, USA.
² The Institute of Ophthalmology, University College London, London, England, UK.
³ Spencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA.
⁴ Moorfields Eye Hospital, London, England, UK.
⁵ Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
⁷ Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA.
⁸ Bascom Palmer Eye Institute, University of Miami Health System, Miami, FL, USA.
⁹ Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁰ Department of Biological Structure, University of Washington, Seattle, WA, USA.
¹¹ Department of Neuroscience, University of Montreal, Montreal, QC, Canada.
¹² University of Montreal Hospital Research Centre, Montreal, QC, Canada.
¹³ Discoveries in Sight Research Laboratories, Devers Eye Institute and Legacy Research Institute, Legacy Health, Portland, OR, USA.
¹⁴ Department of Ophthalmology, Roski Eye Institute, University of Southern California, Los Angeles, CA, USA.
¹⁵ Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, KY, USA.
¹⁶ The Solomon H Snyder, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁷ Departments of Pathology and Cell Biology, Neuroscience, and Ophthalmology, College of Physicians and Surgeons, Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.
¹⁸ Department of Ophthalmology, University of California, San Francisco, CA, USA.
¹⁹ Departments of Ophthalmology and Neurology, University of Pennsylvania, Philadelphia, PA, USA.
²⁰ Department of Ophthalmology and Visual Sciences, Callahan Eye Hospital, University of Alabama at Birmingham, Birmingham, AL, USA.
²¹ Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California, San Diego, CA, USA.
²² Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, 21287 MD, USA.
²³ Departments of Neuroscience, Molecular Biology & Genetics, and Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²⁴ Departments of Neuroscience, Molecular Biology & Genetics, and Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. johnson@jhmi.edu.
²⁵ Cellular & Molecular Medicine Program, Johns Hopkins University School of Medicine, Baltimore, 21287 MD, USA. johnson@jhmi.edu.

^# Contributed equally.

Abstract

Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium's efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies.

Keywords: Glaucoma; Neuroprotection; Ophthalmology; Optic neuropathy; Organoids; Regenerative medicine; Retinal ganglion cells; Stem cells; Transplantation.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain
Cell Differentiation
Humans
Mammals
Optic Nerve Diseases*
Retina
Retinal Ganglion Cells*

Abstract

Publication types

MeSH terms

Grants and funding