{"doi":"10.3390/ijms26178154","title":"RIPK3 Contributes to Thyroid Hormone-Induced Photoreceptor Degeneration","abstract":"Thyroid hormone (TH) regulates cell proliferation, differentiation, and metabolism. Increased TH levels in circulation are associated with a higher incidence of age-related macular degeneration. In mice, TH treatment causes photoreceptor degeneration, which is accompanied by an increase in receptor-interacting serine/threonine-protein kinase 3 (RIPK3) in the retina. Here, we investigated the contribution of RIPK3/necroptosis to TH-induced photoreceptor degeneration using mice deficient in RIPK3 and the necroptotic mixed lineage kinase domain-like protein (MLKL). Wild-type (C57BL/6) and mutant mice at postnatal day 30 received triiodothyronine (T3, 20 µg/mL in drinking water) for four weeks, followed by the evaluation of photoreceptor survival/death and retinal function. Deletion of Ripk3 preserved photoreceptor integrity against T3-induced degeneration, evidenced by improved retinal morphology, increased cone density, improved retinal light responses, and reduced cell death. This protection was observed in both global and photoreceptor-specific Ripk3 knockout mice. In contrast, the deletion of Mlkl did not protect photoreceptors. This work supports the view that RIPK3, but not MLKL, contributes to TH-induced photoreceptor degeneration. The lack of protection from Mlkl deletion suggests that RIPK3’s action is likely mediated via a necrosome-independent mechanism. These findings provide significant insight into how TH signaling induces photoreceptor degeneration and implicate RIPK3 as a potential therapeutic target.","journal":"International Journal of Molecular Sciences","year":2025,"id":534522,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1284157,"name":"Hongwei Ma","orcid":"0000-0002-3344-6549","position":1,"is_corresponding":false},{"id":890780,"name":"Yun Le","orcid":"0000-0002-8853-3981","position":2,"is_corresponding":false},{"id":451313,"name":"Courtney T. Griffin","orcid":"0000-0001-8100-3171","position":3,"is_corresponding":false},{"id":1302030,"name":"Xi-Qin Ding","orcid":null,"position":4,"is_corresponding":false},{"id":1417660,"name":"Lilliana R. York","orcid":null,"position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T02:51:47.434742Z","pmid":"40943078","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":[]}