Hereditary Optic Neuropathies: A New Perspective - Volume II

Building on the success of the Research Topic Hereditary Optic Neuropathies: A New Perspective (with articles spanning genetics, disease modeling, and gene therapy outcomes), the launch of this second volume aims to capture the next wave of actionable advances in the diagnosis, mechanistic understanding, and treatment of hereditary optic neuropathies.Hereditary optic neuropathies (HONs) are a heterogeneous group of optic nerve disorders predominantly caused by mitochondrial dysfunction arising from mitochondrial or nuclear gene defects. Leber hereditary optic neuropathy (LHON) and OPA1-related dominant optic atrophy (DOA) are the most common forms, but next-generation sequencing has rapidly expanded the known genetic spectrum of isolated and syndromic diseases. Challenges remain in interpreting genetic variants, predicting phenotype, and identifying patients within the therapeutic window. Advances in deep phenotyping, electrophysiology, optical coherence tomography (OCT), OCT-angiography (OCT-A), induced pluripotent stem cells (iPSCs), and organoid models have improved understanding of retinal ganglion cell (RGC) vulnerability and disease progression. Notably, some patients show a structural-functional mismatch, with severe RGC loss but only minor functional disturbances, while others present HONs with concomitant retinal and optic nerve dysfunction, underscoring the need for more integrated diagnostic approaches. Furthermore, in recent years, new therapeutic approaches, including gene therapy and gene editing for both LHON and DOA, became available, giving hope for patients.As a continuation of the first volume, this second Research Topic aims to extend that perspective by gathering further contributions on the genetic definition, clinical phenotyping, pathogenic mechanisms, and therapeutic options for HONs, with a focus on diagnosis and management. It will address how genomic and multi-layered imaging technologies improve diagnostic accuracy, how structural and functional findings relate to one another, and how disease models and emerging therapies, including gene therapy, can be translated into clinical practice. The role of artificial intelligence (AI) in reshaping clinical management will also be explored.We welcome submissions across a diverse range of manuscript types supported by the journal - including Original Research, Brief Research Reports, Perspectives, Protocols, Mini-Reviews, and more - exploring, but not limited to, the following themes:- Advances in the field of HONs, from LHON to DOA and beyond- New genes associated with isolated and syndromic optic atrophy, in mitochondrial dynamics (AFG3L2, SPG7, OPA3, SLC25A46) and beyond (RTN4IP1, TMEM126A, ACO2, SSBP1)- Mitochondrial dysfunction and inter-organelle cross-talk underlying disease mechanisms in HONs, from primary forms (LHON, OPA1-related DOA) to other HONs such as Wolfram syndrome and related disorders- Pathophysiology of HONs, including compensatory strategies (mitobiogenesis) and environmental triggers- Structure-function dissociation, i.e., discordance between structural alterations of RGCs/inner retina and the degree of functional impairment - Hereditary forms with concomitant retina and optic nerve dysfunction- Natural history, progression biomarkers, and clinically relevant outcome measures - Selective vulnerability and resilience of different RGC subtypes, including melanopsin-expressing RGCs- iPSC/organoid models in HONs- Deep clinical phenotyping in HONs- The role of electrophysiology in HONs- What visual recovery means in HONs: mechanisms to restore vision- Therapeutic options, including gene therapy- AI-based diagnostic approaches applied to HONs- Future directions towards personalized medicine in HONsArticles will be published online as soon as they are accepted after peer review and approved for publication.Sign up now to participate in this exciting Research Topic.Topic Editor Chiara La Morgia has been serving as principal investigator and site investigator for clinical trials sponsored by GenSight Biologics, Stoke Therapeutics, Reneo, OMEICOS Therapeutics, and Abliva. Topic editors: Chiara La Morgia, Marco Battista, Rustum Karanjia Source: https://www.frontiersin.org/research-topics/85129/hereditary-optic-neuropathies-a-new-perspective---volume-ii