Optic neuritis and autoimmune optic neuropathies: advances in diagnosis and treatment

The Lancet Neurology, Год журнала: 2022, Номер 22(1), С. 89 - 100

Опубликована: Сен. 22, 2022

Язык: Английский

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Imaging of the optic nerve: technological advances and future prospects

The Lancet Neurology, Год журнала: 2022, Номер 21(12), С. 1135 - 1150

Опубликована: Сен. 22, 2022

Язык: Английский

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Randomized trial of bilateral gene therapy injection for m.11778G>A MT-ND4 Leber optic neuropathy

Brain, Год журнала: 2022, Номер 146(4), С. 1328 - 1341

Опубликована: Ноя. 7, 2022

Leber hereditary optic neuropathy (LHON) is an important example of mitochondrial blindness with the m.11778G>A mutation in MT-ND4 gene being most common disease-causing mtDNA variant worldwide. The REFLECT phase 3 pivotal study a randomized, double-masked, placebo-controlled trial investigating efficacy and safety bilateral intravitreal injection lenadogene nolparvovec patients confirmed mutation, using recombinant adeno-associated virus vector 2, serotype 2 (rAAV2/2-ND4). first-affected eye received therapy; fellow (affected/not-yet-affected) was randomly injected therapy or placebo. primary end point difference change from baseline best-corrected visual acuity (BCVA) second-affected/not-yet-affected eyes treated versus placebo at 1.5 years post-treatment, expressed logarithm minimal angle resolution (LogMAR). Forty-eight were bilaterally 50 unilaterally. At years, BCVA not statistically different between receiving (primary point). A significant improvement reported to nolparvovec-treated eyes: -0.23 LogMAR for (P < 0.01); -0.15 unilaterally 0.05). mean nadir -0.38 (0.052) -0.33 nolparvovec, respectively (bilateral treatment group). (0.051) -0.26 observed placebo-treated eyes, (unilateral proportion one both on-chart 85.4% 72.0% patients, respectively. well tolerated, no systemic issues. Intraocular inflammation, which mostly mild controlled topical corticosteroids, occurred 70.7% 10.2% eyes. Among there incidence intraocular inflammation patients. Overall, demonstrated LHON carrying degree natural history studies supports improved benefit/risk profile injections relative unilateral injections.

Язык: Английский

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Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial

Cell Reports Medicine, Год журнала: 2024, Номер 5(3), С. 101437 - 101437

Опубликована: Фев. 29, 2024

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown be effective in stabilizing restoring patients treated within 1 year of onset The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy safety idebenone treatment (900 mg/day) with LHON up 5 years after symptom (N = 199) over period 24 months, compared an external history control cohort 372), matched by time since onset. meets its primary endpoint confirms long-term subacute/dynamic chronic phases; effect varies depending on phase causative mtDNA mutation. findings will help guide clinical management LHON.

Язык: Английский

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Mitochondrial optic neuropathies

Handbook of clinical neurology, Год журнала: 2023, Номер unknown, С. 23 - 42

Опубликована: Янв. 1, 2023

Язык: Английский

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Mitochondrial retinopathies and optic neuropathies: the impact of retinal imaging on modern understanding of pathogenesis, diagnosis, and management

Progress in Retinal and Eye Research, Год журнала: 2024, Номер 101, С. 101264 - 101264

Опубликована: Май 3, 2024

Язык: Английский

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Optic nerve diseases and regeneration: How far are we from the promised land?

Clinical and Experimental Ophthalmology, Год журнала: 2023, Номер 51(6), С. 627 - 641

Опубликована: Июнь 15, 2023

Abstract The retinal ganglion cells (RGCs) are the sole output neurons that connect information from retina to brain. Optic neuropathies such as glaucoma, trauma, inflammation, ischemia and hereditary optic neuropathy can cause RGC loss axon damage, lead partial or total of vision, which is an irreversible process in mammals. accurate diagnoses crucial for timely treatments prevent irrevocable RGCs loss. After severe ON damage neuropathies, promoting regeneration vital restoring vision. Clearance neuronal debris, decreased intrinsic growth capacity, presence inhibitory factors have been shown contribute failure post‐traumatic CNS regeneration. Here, we review current understanding manifestations various common neuropathies. We also summarise known mechanisms survival mammals, including specific signalling pathways, key transcription factors, reprogramming genes, inflammation‐related stem cell therapy, combination therapies. Significant differences subtypes regenerative capacity after injury found. Finally, highlight developmental states non‐mammalian species capable regenerating axons injury, cellular state neural repair.

Язык: Английский

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Mitochondria and the eye—manifestations of mitochondrial diseases and their management

Eye, Год журнала: 2023, Номер 37(12), С. 2416 - 2425

Опубликована: Апрель 25, 2023

Abstract Historically, distinct mitochondrial syndromes were recognised clinically by their ocular features. Due to predilection for metabolically active tissue, diseases frequently involve the eye, resulting in a range of ophthalmic manifestations including progressive external ophthalmoplegia, retinopathy and optic neuropathy, as well deficiencies retrochiasmal visual pathway. With wider availability genetic testing clinical practice, it is now that genotype-phenotype correlations can be imprecise: many classic associated with multiple genes variants, same variant have presentations, subclinical individuals who are otherwise asymptomatic. Previously considered rare no effective treatments, considerable progress has been made our understanding new therapies emerging, particular, gene therapy inherited neuropathies.

Язык: Английский

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Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

Neural Regeneration Research, Год журнала: 2024, Номер 20(2), С. 587 - 597

Опубликована: Янв. 31, 2024

JOURNAL/nrgr/04.03/01300535-202502000-00034/figure1/v/2024-05-28T214302Z/r/image-tiff Several studies have found that transplantation of neural progenitor cells (NPCs) promotes the survival injured neurons. However, a poor integration rate and high risk tumorigenicity after cell limits their clinical application. Small extracellular vesicles (sEVs) contain bioactive molecules for neuronal protection regeneration. Previous shown stem/progenitor cell-derived sEVs can promote recovery neurological function in neurodegenerative eye diseases other diseases. In this study, we intravitreally transplanted derived from human induced pluripotent stem (hiPSCs) hiPSCs-differentiated NPCs (hiPSC-NPC) mouse model optic nerve crush. Our results show these injected were ingested by retinal cells, especially those localized ganglion layer. Treatment with hiPSC-NPC-derived mitigated crush-induced degeneration, regulated microenvironment inhibiting excessive activation microglia. Component analysis further revealed hiPSC-NPC transported neuroprotective anti-inflammatory miRNA cargos to target which had protective effects on RGCs injury. These findings suggest are promising cell-free therapeutic strategy neuropathy.

Язык: Английский

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Comparison of Brn3a and RBPMS Labeling to Assess Retinal Ganglion Cell Loss During Aging and in a Model of Optic Neuropathy

Investigative Ophthalmology & Visual Science, Год журнала: 2024, Номер 65(4), С. 19 - 19

Опубликована: Апрель 8, 2024

Purpose: Retinal ganglion cell (RGC) loss provides the basis for diagnosis and stage determination of many optic neuropathies, quantification RGC survival is a critical outcome measure in models neuropathy. This study examines accuracy manual counting using two selective markers, Brn3a RBPMS. Methods: flat mounts from 1- to 18-month-old C57BL/6 mice, mice after microbead (MB)-induced intraocular pressure (IOP) elevation, are immunostained with and/or RBPMS antibodies. Four individuals masked experimental conditions manually counted labeled RGCs three copies five images, inter- intra-person reliability was evaluated by intraclass correlation coefficient (ICC). Results: A larger population (approximately 10% higher) than antibody up 6 months age, but differences decrease approximately 1% at older ages. Both RGC-labeled populations significantly age. MB-induced IOP elevation associated significant both Brn3a- RBPMS-positive RGCs. Notably, labeling more consistent counts interpersonal (ICC = 0.87 0.11, respectively) intra-personal 0.97 0.66, respectively). Conclusions: markers independently capable detecting decreases number age response despite RPBMS less prone variability labeling. Overall, either marker can be used as single detect changes survival, each offering distinct advantages.

Язык: Английский

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