Functional Rescue in Retinal Degeneration: Editing Photoreceptor and RPE Pathways, Ion Channels, and Ciliopathy Genes

Retinal degenerations remain a leading cause of irreversible blindness, driven by diverse genetic lesions that disrupt photoreceptor and retinal pigment epithelium (RPE) function, synaptic integrity, and cellular homeostasis. The advent of precision genome and RNA editing—spanning CRISPR/Cas nucleases, base and prime editors, RNA-targeting systems, and epigenome modulators—offers a powerful toolkit to restore vision by correcting causal variants, reprogramming dysfunctional pathways, and stabilizing cellular phenotypes. This Research Topic invites original research, methods, perspectives, and reviews that advance functional rescue in inherited retinal disease (IRD) by targeting photoreceptor and RPE pathways, ion channel function, and ciliopathy-associated genes.

We particularly welcome work that:

1. Designs and validates editing strategies for phototransduction components, RPE metabolic and phagocytic pathways, and outer segment maintenance.

2. Restores ion channel function (e.g., KCNJ13 and related channelopathies), synaptic transmission, or calcium/ion homeostasis in rod, cone, and RPE cells.

3. Addresses ciliopathy genes impacting cilium structure and trafficking, linking genotype correction to measurable rescue of ciliary architecture and function.

4. Benchmarks on-target efficacy, allele specificity, off-target/indel profiles, and transcriptomic/epigenomic consequences with clinically relevant assays.

5. Develops delivery modalities suited for retinal targets (RNP, nonviral vectors, compact editors), with intravitreal, subretinal, or suprachoroidal approaches optimized for cell-type selectivity and durability.

6. Demonstrates translational endpoints, including electrophysiology, optokinetic/behavioral vision assays, high-resolution imaging, and long-term safety and immunogenicity.

7. Explores editing of dominant-negative, haploinsufficient, or complex alleles using knock-in, knockdown-and-replace, read-through, or base/prime editing frameworks.

Submissions spanning model systems—from human iPSC-derived retinal organoids and RPE, to zebrafish, murine, and large-animal models—are encouraged, as are computational tools for guide design, delivery optimization, and potency prediction.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Policy Brief
• Review
• Systematic Review

Keywords: Retinal degeneration, Genome and RNA editing, Photoreceptor and RPE rescue, Ion Channelopathies, Ciliopathy genes and ciliary trafficking

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.