Send Comments to IFOND

International Foundation for Optic Nerve Disease

Funding research and disseminating information on causes, prevention and treatment.
Welcome | Impact | Glaucoma | LHON | Toxic | Ischaemic | Projects | Donors | Coping | Glossary | Links | Use | About | Contact | Donate
IFOND Dictionary: Index | A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | NUM

IFOND research | LHON treatment prospects | Mitochondrial Genome Editing | COVID-19 and LHON | LHON talks | Pay it forward | Mitochondrial Regulation | Avoid BAK eye drop preservative, etc. | We experiment with cigarette smoke so you need not. | Viral vector trials | EPI-743 LHON trials | Idebenone LHON trials

Digests: NEI News | Mitochondrial Disease News LHON | ARVO Journals LHON | PubMed LHON | Europe PMC LHON | MRC-MBU news

Note: the posting or linking of research, news, information or forum articles on this site does not mean that any proposed treatment methods are accepted or safe. Material posted here is FOR INFORMATION ONLY, and the INFORMATION CONTAINED THEREIN IS NOT AN ENDORSEMENT BY IFOND. If you seek treatment or preventative guidance, discuss this with your personal health professional.

Reviews of LHON treatment prospects

Listed in references below are important reviews of the research and treatment prospects in Leber Hereditary Optic Neuropathy [LHON].

Editor comments:

In 2022 Spiegel and Sadun offered an Overview of Current and Future Treatment Strategies in Leber's Hereditary Opic Neuropathy. They outline their current understanding of the disease, therapies, past, current and potential and suggest research paths.

The 2020 review by Bahr et al is broad, thorough and refreshing in its clear outline of the issues at hand. It emphasised the unique nature of the susceptible retinal ganglion cells [RGC] in LHON. It points out the lack of an established proven detailed pathophysiology of LHON in spite of human treatment trials already being performed. Thus, there is a requirement to do research on appropriate models, for example based on human induced pluripotential stem cell technology, of these particular types of RGCs and even on RGCs which are from genetic individuals. A broad range of research questions and approaches is suggested.

Vianello et al [including IFOND board member Dr Carelli] in 2020 explore the Interaction between Mitochondrial DNA Variants and Mitochondria/Endoplasmic Reticulum Contact Sites [MERCS]. MERCS are a fundamental, yet under explored element in mitochondrial regulation likely relevant to the pathophysiology of various mitochondrial diseases. PMID:32598172.

The incomplete loss of vision in those affected by LHON and the anecdotes of partial or complete visual recovery in LHON and other optic nerve and visual system insults gives hope for rehabilitation of the visual system in LHON. One recovery pathway may be to better understand and exploit the neuroplasticity of the central nervous system. Reviews of this area of active research are below.

Somewhat against the grain of the narrow drug centred 'silver bullet' paradigm currently dominating medical research and therapy is another call for long overdue research on the safety and efficacy of diet therapy. For example, not enough research on ketogenic diets in LHON has occurred since Douglas Wallace's proposal in 2010, 'Mitochondrial Energetics and Therapeutics', where he outlines and critiques metabolic therapies for mitochondrial diseases to date and discusses the revival of ketogenic diets and a more systemic approach as potential therapy. This approach is gaining popularity in many major diseases. So it is important for LHON carriers to know if this approach is safe for them and possibly preventative for various illness including LHON. Maybe a mouse fodder trial is the next step? Maybe survey of insulin resistance in LHON carriers and affected? Coffee anyone? Since we know Efficient mitochondrial biogenesis drives incomplete penetrance in Leber’s hereditary optic neuropathy, shouldn't we find all avenues to support it?

Absent from the retinal ganglion cell literature so far are relatively new concepts of biomolecular condensates and intracellular phase separation affected by interfacial water and mitochondrial matrix viscosity. Various light spectra and melatonin are known to affect these parameters. Research in dementia exploring these mechanisms may be relevant.

Some research on the benefits of ketosis on the optic nerve and nervous system (then caution followed by coffee):

Storoni M, Robert MP, Plant GT. The therapeutic potential of a calorie-restricted ketogenic diet for the management of Leber hereditary optic neuropathy. Nutr Neurosci. 2019 Mar;22(3):156-164. doi: 10.1080/1028415X.2017.1368170. Epub 2017 Oct 10. PMID:28994349 DOI: 10.1080/1028415X.2017.1368170

Zarnowski T, Tulidowicz-Bielak M, Zarnowska I, Mitosek-Szewczyk K, Wnorowski A, Jozwiak K, Gasior M, Turski WA. Kynurenic Acid and Neuroprotective Activity of the Ketogenic Diet in the Eye. Curr Med Chem. 2017;24(32):3547-3558. doi: 10.2174/0929867324666170509120257. PMID: 28486923 DOI: 10.2174/0929867324666170509120257

Harun-Or-Rashid M, Pappenhagen N, Palmer P, Smith MA, Gevorgyan V, Wilson GN, Crish SD, Inman DM. Structural and Functional Rescue of Chronic Metabolically Stressed Optic Nerves through Respiration. J Neurosci. 2018 May 30;38(22):5122-5139. doi: 10.1523/JNEUROSCI.3652-17.2018. Epub 2018 May 14. PMID: 29760184 PMCID: PMC5977447 DOI: 10.1523/JNEUROSCI.3652-17.2018

Sonia Emperador, Ester López-Gallardo, Carmen Hernández-Ainsa, Mouna Habbane, Julio Montoya, M. Pilar Bayona-Bafaluy & Eduardo Ruiz-Pesini. Orphanet Journal of Rare Diseases volume 14, Article number: 150 (2019). Ketogenic treatment reduces the percentage of a LHON heteroplasmic mutation and increases mtDNA amount of a LHON homoplasmic mutation.

Pflanz NC, Daszkowski AW, James KA, Mihic SJ. Ketone body modulation of ligand-gated ion channels. Neuropharmacology. 2019 Apr;148:21-30. doi: 10.1016/j.neuropharm.2018.12.013. Epub 2018 Dec 15. PMID 30562540 DOI: 10.1016/j.neuropharm.2018.12.013

Hasan-Olive MM, Lauritzen KH, Ali M, Rasmussen LJ, Storm-Mathisen J, Bergersen LH. A Ketogenic Diet Improves Mitochondrial Biogenesis and Bioenergetics via the PGC1α-SIRT3-UCP2 Axis. Neurochem Res. 2019 Jan;44(1):22-37. doi: 10.1007/s11064-018-2588-6. Epub 2018 Jul 19. PMID 30027365

Bajracharya R1, Youngson NA2, Ballard JWO3. Dietary Macronutrient Management to Treat Mitochondrial Dysfunction in Parkinson's Disease. Int J Mol Sci. 2019 Apr 15;20(8). pii: E1850. doi: 10.3390/ijms20081850. PMC6514887

Hanyuda A, Rosner BA, Wiggs JL, et al. Low-carbohydrate-diet scores and the risk of primary open-angle glaucoma: data from three US cohorts. Eye (Lond). 2020;34(8):1465-1475. doi:10.1038/s41433-020-0820-5 PMCID: PMC7470850

Lauritzen KH, Hasan-Olive MM, Regnell CE, Kleppa L, Scheibye-Knudsen M, Gjedde A, Klungland A, Bohr VA, Storm-Mathisen J, Bergersen LH. A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain. Neurobiol Aging. 2016 Dec;48:34-47. doi: 10.1016/j.neurobiolaging.2016.08.005. Epub 2016 Aug 18.

Vandenberghe C, St-Pierre V, Courchesne-Loyer A, Hennebelle M, Castellano CA, Cunnane SC. Caffeine intake increases plasma ketones: an acute metabolic study in humans. Can J Physiol Pharmacol. 2017 Apr;95(4):455-458. doi: 10.1139/cjpp-2016-0338. Epub 2016 Nov 25. PMID 28177691

LHON Reviews:

Miller NR, Tsai RK. Optic Neuropathies: Current and Future Strategies for Optic Nerve Protection and Repair. Int J Mol Sci. 2023 Apr 10;24(8):6977. doi: 10.3390/ijms24086977. PMID: 37108140; PMCID: PMC10139137.

Spiegel SJ, Sadun AA. Solutions to a Radical Problem: Overview of Current and Future Treatment Strategies in Leber's Hereditary Opic Neuropathy. Int J Mol Sci. 2022 Oct 30;23(21):13205. doi: 10.3390/ijms232113205. PMID: 36361994; PMCID: PMC9656544.

Catarino, Claudia B. MD, PhD; von Livonius, Bettina MD; Priglinger, Claudia MD; Banik, Rudrani MD; Matloob, Selma MBChB, MRCOphth; Tamhankar, Madhura A. MD; Castillo, Lorena MD; Friedburg, Christoph MD, FEBO; Halfpenny, Christopher A. MBBS, PhD; Lincoln, John A. MD, PhD; Traber, Ghislaine L. MD; Acaroglu, Gölge MD; Black, Graeme C. M. DPhil, FRCOphth; Doncel, Carlos MD; Fraser, Clare L. MBBS, MMed; Jakubaszko, Joanna MD, PhD; Landau, Klara MD, FEBO; Langenegger, Stefan J. MD, FEBO; Muñoz-Negrete, Francisco J. MD, PhD; Newman, Nancy J. MD; Poulton, Joanna DM, MRCPCH; Scoppettuolo, Elisabetta MBBS, FRCOphth; Subramanian, Prem MD, PhD; Toosy, Ahmed T. MBBS, FRCP; Vidal, Mariona MD; Vincent, Andrea L. MBChB, MD; Votruba, Marcela BM BCh, FRCOphth; Zarowski, Marcin MD, PhD; Zermansky, Adam MBChB, FRCP; Lob, Felice MD; Rudolph, Günther MD; Mikazans, Oskars MA; Silva, Magda; Llòria, Xavier MD; Metz, Günther PhD; Klopstock, Thomas MD Real-World Clinical Experience With Idebenone in the Treatment of Leber Hereditary Optic Neuropathy, Journal of Neuro-Ophthalmology: September 22, 2020 - Volume Publish Ahead of Print - Issue - doi: 10.1097/WNO.0000000000001023

Newman NJ, Carelli V, Taiel M, Yu-Wai-Man P. Visual Outcomes in Leber Hereditary Optic Neuropathy Patients With the m.11778G>A (MTND4) Mitochondrial DNA Mutation. J Neuroophthalmol. 2020 Sep 21. doi: 10.1097/WNO.0000000000001045. Epub ahead of print. PMID: 32969847.

Vianello C, Cocetta V, Caicci F, Boldrin F, Montopoli M, Martinuzzi A, Carelli V, Giacomello M. Interaction Between Mitochondrial DNA Variants and Mitochondria/Endoplasmic Reticulum Contact Sites: A Perspective Review. DNA Cell Biol. 2020 Aug;39(8):1431-1443. doi: 10.1089/dna.2020.5614. Epub 2020 Jun 26. PMID: 32598172.

B Domènech E, Marfany G. The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies. Antioxidants (Basel). 2020 Apr 23;9(4):347. doi: 10.3390/antiox9040347. PMID: 32340220; PMCID: PMC7222416.

Mejia-Vergara AJ, Seleme N, Sadun AA, Karanjia R. Pathophysiology of Conversion to Symptomatic Leber Hereditary Optic Neuropathy and Therapeutic Implications: a Review. Curr Neurol Neurosci Rep. 2020;20(5):11. Published 2020 Apr 15. doi:10.1007/s11910-020-01032-8 PMID: 32296973

Shemesh A, Sood G, Margolin E. Leber Hereditary Optic Neuropathy (LHON). In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 17, 2020. PMID: 29494105

Tyler Bahr, Kyle Welburn, Jonathan Donnelly, Yidong Bai. Emerging model systems and treatment approaches for Leber's hereditary optic neuropathy: Challenges and opportunities Biochim Biophys Acta Mol Basis Dis. 2020 Jun 1;1866(6):165743. doi: 10.1016/j.bbadis.2020.165743. Epub 2020 Feb 24. PMID: 32105823 DOI: 10.1016/j.bbadis.2020.165743

In Current and Emerging Treatment Modalities for Leber’s Hereditary Optic Neuropathy: A Review of the Literature. Adv Ther. 2018; 35(10): 1510–1518. The authors review the literature and summarize treatment trials.

In Leber Hereditary Optic Neuropathy— Light at the End of the Tunnel? Asia-Pacific Journal of Ophthalmology Volume 7, Number 4, July/August 2018. Ungsoo Samuel Kim, MD, PhD, Neringa Jurkute, MD, FEBO, and our IFOND board member Patrick Yu-Wai-Man, PhD, FRCOphth, outline modes of Mitochondrial protection, Mitochondrial biogenesis, Gene Therapy, Mitochondrial replacement therapy, and Pluripotent Stem cell therapy.

Neringa Jurkutea and Patrick Yu-Wai-Man. Leber hereditary optic neuropathy: bridging the translational gap. Curr Opin Ophthalmol. 2017 Sep; 28(5): 403–409. Published online 2017 Aug 10. doi: 10.1097/ICU.0000000000000410 PMCID: PMC5562441 PMID: 28650878

Is there treatment for Leber Hereditary Optic Neuropathy? Curr Opin Ophthalmol. 2015 Nov; 26(6): 450–457. Jason H. Peragallo, MD and Nancy J. Newman, MD review treatment.

Meyerson C, Van Stavern G, McClelland C. Leber hereditary optic neuropathy: current perspectives. Clin Ophthalmol. 2015;9:1165-1176 doi: 10.2147/OPTH.S62021.

Mitochondrial optic neuropathies: our travels from bench to bedside and back again. Alfredo A Sadun MD PhD Chiara La Morgia MD PhD Valerio Carelli MD PhD Clinical and Experimental Ophthalmology. Royal Australian and New Zealand College of Ophthalmologists. First published: 21 February 2013.

Mitochondrial disease reviews:

Loh, D.; Reiter, R.J. Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia. Int. J. Mol. Sci. 2023, 24, 5835.

Carelli V, La Morgia C. Clinical syndromes associated with mtDNA mutations: where we stand after 30 years. Essays Biochem. 2018 Jul 20;62(3):235-254. doi: 10.1042/EBC20170097. Print 2018 Jul 20. PMID:30030360

Michio Hirano, Valentina Emmanuele, and Catarina M Quinzii. Emerging Therapies for Mitochondrial Diseases. Essays Biochem. 2018 Jul 20; 62(3): 467–481. Published online 2018 Jul 20. doi: 10.1042/EBC20170114 PMCID: PMC6104515 NIHMSID: NIHMS984793 PMID: 29980632 PMC6104515

Valero T. Mitochondrial biogenesis: pharmacological approaches. Curr Pharm Des. 2014;20(35):5507-9. DOI: 10.2174/138161282035140911142118 PMID: 24606795

Banani SF, Lee HO, Hyman AA, Rosen MK. Biomolecular condensates: organizers of cellular biochemistry. Nat Rev Mol Cell Biol. 2017 May;18(5):285-298. doi: 10.1038/nrm.2017.7. Epub 2017 Feb 22. PMID: 28225081; PMCID: PMC7434221.

Neuroplasticity reviews:

Sabel BA, Gao Y, Antal A. Reversibility of visual field defects through induction of brain plasticity: vision restoration, recovery and rehabilitation using alternating current stimulation. Neural Regen Res. 2020 Oct;15(10):1799-1806. doi: 10.4103/1673-5374.280302. PMID: 32246620.

Castaldi E, Lunghi C, Morrone MC. Neuroplasticity in adult human visual cortex. Neurosci Biobehav Rev. 2020 May;112:542-552. doi: 10.1016/j.neubiorev.2020.02.028. Epub 2020 Feb 21. PMID: 32092315.

IFOND welcomes questions and comments
Welcome | Impact | Glaucoma | LHON | Toxic | Ischaemic | Projects | Donors | Coping | Glossary | Links | Use | About | Contact | Donate

Donate to IFOND sponsored research. You can designate which area of current IFOND activities to direct your funds:
>> Donate online <<
donate directly to IFOND at the address below:

The International Foundation for Optic Nerve Disease
P. O. Box 777, Cornwall NY 12518, USA.
Phone/Fax: (845)5348606
Web site:

IFOND is registered service mark of The International Foundation for Optic Nerve Disease, est. October 1995.

Copyright 1999-2024, International Foundation for Optic Nerve Disease.

The information contained on this website should not be considered medical guidance or professional advice. IFOND is not responsible for errors or omissions in information provided on this site or actions resulting from its use. IFOND does not publish all information from all available sources on optic nerve disease. IFOND is not responsible for the validity of the studies or reviews nor is it an advocate of studies or reviews mentioned on or linked from the IFOND web site. IFOND does not endorse or recommend participation in any particular clinical trial or treatment protocol which may be mentioned on this site. Direct any questions concerning your personal health to your appropriate health care professional.