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

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: Sept. 21, 2023

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

Language: Английский

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Zebrafish optic nerve injury results in systemic retinal ganglion cell dedifferentiation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Abstract Retinal ganglion cells (RGCs) are the sole projection neurons connecting retina to brain and therefore play a critical role in vision. Death of RGCs during glaucoma, optic neuropathies after ocular trauma results irreversible loss vision as do not regenerate human eye. Moreover, there no FDA approved therapies that prevent RGC death and/or promote survival diseased or injured There is need better understand molecular underpinnings neuroprotection develop effective therapeutic approaches preserve damaged RGCs. Unlike mammals, zebrafish resilient nerve injury, even complete transection nerve. Here, we leveraged this unique model utilized single-cell RNA sequencing characterize responses injury identify putative neuroprotective regenerative pathways. heterogeneous studies mice have shown differential resiliency across subtypes. Our demonstrated all subtypes zebrafish. Quantifying changes gene expression revealed upregulation progenitor markers well distinct early late phases response. This shift causes injury-responsive resemble subtype 3, low frequency population endogenous immature normally maintained wild-type, uninjured adult retina. A similar but restricted transcriptomic response contralateral eye was also detected, highlighting systemic unilateral injury. Taken together, these demonstrate dedifferentiate may be novel mechanism mediating their cell capabilities. Author Summary connect essential for Their conditions like affecting over 70 million people worldwide, leads permanent blindness, with FDA-approved treatments it. In study, used next-generation technologies at level. We discovered survive damage by temporarily shifting into less mature state, resembling rare found animals. identified many genes whose RGCs, work significant because our detailed characterization identifies dedifferentiation an response, possibly important axon regrowth. The pathways potential targets enable

Language: Английский

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Gene Expression and Editing in Mammalian Retinal Ganglion Cells

Essentials in ophthalmology/Essentials ophthalmology, Journal Year: 2024, Volume and Issue: unknown, P. 295 - 327

Published: Jan. 1, 2024

Language: Английский

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Association Between Glaucoma and Brain Structural Connectivity Based on Diffusion Tensor Tractography: A Bidirectional Mendelian Randomization Study

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(10), P. 1030 - 1030

Published: Oct. 17, 2024

Glaucoma is a neurodegenerative ocular disease that accompanied by cerebral damage extending beyond the visual system. Recent studies based on diffusion tensor tractography have suggested an association between glaucoma and brain structural connectivity but not clarified causality.

Language: Английский

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