{"doi":"10.3389/fcell.2023.1301279","title":"Editorial: Inherited retinal dystrophies: a light at the end of the tunnel?","abstract":"Once genetic variants are deemed pathogenic, additional work is necessary to explain disease mechanisms. Jones et al. describe the complementary use of human pluripotent stem cell retinal organoids and preclinical mouse models to investigate the role of DRAM2 in conerod dystrophy. The DRAM2 gene encodes a transmembrane protein with poorly defined cellular function. Mutations in DRAM2 lead to a rare form of age-related maculopathy but the details of disease progression remained unclear. The authors discuss how different disease models can be leveraged to study disease progression and the advantages and caveats of making comparisons between human stem cell-derived organoids and mouse models.Three papers describe efforts to uncover the molecular mechanisms driving photoreceptor dysfunction and vision loss. Sadeh et al. explored the impact of 10 distinct disease-causing missense mutations in the CACNA1F gene, which encodes the Cav1.4α1 calcium channel. Using a combination of molecular modeling, patch-clamp analysis, and protein stability assays, the authors discovered that mutations in this calcium channel altered protein structure and decreased ion current through the mutant channels. Importantly, they discovered that the mutant proteins were degraded by the proteosome and that inhibition of proteosome machinery could partially restore channel function, suggesting a potential therapeutic option for individuals with congenital stationary night blindness. Radhakrishnan and colleagues sought to determine the binding domain in the receptor retinol binding protein 4 receptor 2 (RBPR2) protein for the ligand retinol binding protein 4 (RBP4). RBP4 binds to alltrans-retinol (ROL) in the bloodstream and transports ROL to cells throughout the body. ROL is the major form of vitamin A within the bloodstream and serves as the precursor to 11-cis retinaldehyde, which is the vitamin A derivative essential for light detection. RBPR2 is a receptor for RBP4 and the absence of RBPR2 leads to vision loss, underscoring the importance of RBPR2 in maintaining ROL homeostasis within the eye. To better understand how RBPR2 binds to RBP4, the authors utilized molecular modeling and biochemical binding assays to interrogate specific amino acid changes in RPBR2 and to identify a critical binding domain for RBP4. Finally, Linnert et al. sought to identify interacting partners for ADGRV1 and CIB2, two proteins which when mutated cause Usher Syndrome. Using affinity proteomics and biochemical assays, the authors discovered that these USH proteins shared numerous interacting proteins and, unexpectedly, interacted with proteins of the Bardet Biedl Syndrome (BBS) complex. These data suggest that USH and BBS may share similar pathogenic mechanisms that lead to vision loss.Given the clinical and genetic heterogeneity of IRDs, the development of regenerative medicine strategies could provide treatments that are not specific to a particular mutation or even a specific gene. To this end, Boyd et al. explore the role of cardiotrophin-like cytokine factor 1 (Clcf1) and cytokine receptor-like factor 1a (Crlf1a) to induce Muller glia to proliferate in the zebrafish retina. The zebrafish has an innate ability to regenerate retinal cells following injury. By leveraging knowledge of how this process is regulated in zebrafish, regenerative strategies for humans with IRDs may be developed. Other gene-agnostic approaches may include mitigating the effect of inflammation. Sarici et al. use retrospective clinical data to demonstrate that managing inflammation in IRDs can potentially mitigate disease progression regardless of the genetic mutation. Such efforts may prolong the window of opportunity for bespoke gene therapy interventions.In conclusion, this research topic provides current insights into the complexities faced by clinicians and researchers in accurately diagnosing and investigating the pathomechanisms of IRDs. This collection should benefit investigators interested in","journal":"Frontiers in Cell and Developmental Biology","year":2023,"id":412236,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":399983,"name":"Glenn P. Lobo","orcid":"0000-0003-2698-1989","position":1,"is_corresponding":false},{"id":399978,"name":"Altaf A. Kondkar","orcid":"0000-0002-5516-6951","position":2,"is_corresponding":false},{"id":510626,"name":"José M. Millán","orcid":"0000-0002-7211-9129","position":3,"is_corresponding":false},{"id":399982,"name":"Brian D. Perkins","orcid":"0000-0002-9348-6542","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T01:21:50.261851Z","pmid":"37860821","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}