D'Esposito Fabiana, Zeppieri Marco, Cordeiro Maria Francesca, Capobianco Matteo, Avitabile Alessandro, Gagliano Giuseppe, Musa Mutali, Barboni Piero, Gagliano Caterina
Imperial College Ophthalmic Research Group (ICORG) Unit, Imperial College, London NW1 5QH, UK.
Eye Clinic, Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples Federico II, 80131 Naples, Italy.
Genes (Basel). 2024 Nov 29;15(12):1559. doi: 10.3390/genes15121559.
/: Optic neuropathies are a category of illnesses that ultimately cause damage to the optic nerve, leading to vision impairment and possible blindness. Disorders such as dominant optic atrophy (DOA), Leber hereditary optic neuropathy (LHON), and glaucoma demonstrate intricate genetic foundations and varied phenotypic manifestations. This narrative review study seeks to consolidate existing knowledge on the genetic and molecular mechanisms underlying ocular neuropathies, examine genotype-phenotype correlations, and assess novel therapeutic options to improve diagnostic and treatment methodologies. : A systematic literature review was performed in October 2024, utilizing PubMed, Medline, the Cochrane Library, and ClinicalTrials.gov. Search terms encompassed "optic neuropathy", "genetic variants", "LHON", "DOA", "glaucoma", and "molecular therapies". Studies were chosen according to established inclusion criteria, concentrating on the genetic and molecular dimensions of optic neuropathies and their therapeutic ramifications. : The results indicate that DOA and LHON are mostly associated with the mitochondrial dysfunction resulting from pathogenic variants in nuclear genes, mainly , and mitochondrial DNA (mtDNA) genes, respectively. Glaucoma, especially its intricate variants, is linked to variants in genes like , , and . Molecular mechanisms, such as oxidative stress and inflammatory modulation, are pivotal in disease progression. Innovative therapeutics, including gene therapy, RNA-based treatments, and antioxidants such as idebenone, exhibit promise for alleviating optic nerve damage and safeguarding vision. : Genetic and molecular investigations have markedly enhanced our comprehension of ocular neuropathies. The amalgamation of genetic and phenotypic data is essential for customized medical strategies. Additional research is required to enhance therapeutic strategies and fill the gaps in our understanding of the underlying pathophysiology. This interdisciplinary approach shows potential for enhancing patient outcomes in ocular neuropathies.
视神经病变是一类最终会对视神经造成损害、导致视力障碍甚至可能失明的疾病。诸如显性遗传性视神经萎缩（DOA）、Leber遗传性视神经病变（LHON）和青光眼等疾病表现出复杂的遗传基础和多样的表型表现。本叙述性综述研究旨在整合有关眼部神经病变潜在遗传和分子机制的现有知识，研究基因型与表型的相关性，并评估新的治疗选择，以改进诊断和治疗方法。：2024年10月进行了一项系统的文献综述，使用了PubMed、Medline、Cochrane图书馆和ClinicalTrials.gov。检索词包括“视神经病变”“基因变异”“LHON”“DOA”“青光眼”和“分子疗法”。根据既定的纳入标准选择研究，重点关注视神经病变的遗传和分子层面及其治疗影响。：结果表明，DOA和LHON大多分别与核基因（主要是 ）和线粒体DNA（mtDNA）基因中的致病变异导致的线粒体功能障碍有关。青光眼，尤其是其复杂的变异类型，与 、 和 等基因的变异有关。氧化应激和炎症调节等分子机制在疾病进展中起关键作用。创新疗法，包括基因疗法、基于RNA的治疗以及艾地苯醌等抗氧化剂，有望减轻视神经损伤并保护视力。：遗传和分子研究显著提高了我们对眼部神经病变的理解。遗传和表型数据的整合对于定制医疗策略至关重要。需要进一步的研究来改进治疗策略，并填补我们对潜在病理生理学理解的空白。这种跨学科方法在改善眼部神经病变患者的治疗结果方面显示出潜力。
