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Citicoline in glaucoma? Neuroprotection is more than a single active substance.

Explanatory graphic of all micronutrients in Ophtaprotect® SEHNERV and their effects on the mitochondrial respiratory chain, oxidative stress, and the cell membrane.

Micronutrients as adjunctive glaucoma therapy

Citicoline / Lecithin and Coenzyme Q10 are currently in the focus of the ophthalmological community. However, in order to meaningfully assess and therapeutically apply their potential neuroprotective effects in glaucoma, they must be considered in the context of complex neurodegenerative processes. The following section explains key mechanisms such as oxidative stress, neuroinflammation, and intraocular pressure – and, building on this, introduces three micronutrient-based strategies to support the optic nerve.

Oxidative Stress, Neuroinflammation, and Intraocular Pressure: Understanding Neurodegenerative Processes in Glaucoma

To understand the mode of action of the micronutrients in Ophtaprotect® SEHNERV, it is important first to understand the key neurodegenerative mechanisms in glaucoma. The following section describes the interplay of oxidative stress, neuroinflammation, and intraocular pressure before presenting the three neuroprotective strategies to support the optic nerve.

Even in the early stages of glaucoma, metabolic and oxidative stress occurs in the unmyelinated axons of retinal ganglion cells. Oxidative stress and mitochondrial dysfunction are closely linked and can trigger neuroinflammation as well as neurodegeneration. In this process, both mitochondrial and cellular membranes are damaged, ultimately leading to the death of ganglion cells.

These neurodegenerative processes occur partly independently of intraocular pressure, but changes in the trabecular meshwork can also impair the regulation of intraocular pressure (IOP). The trabecular meshwork is constantly exposed to oxidative stress, which can be exacerbated by light, metabolic processes, or inflammation. The resulting reactive oxygen species (ROS) damage the trabecular cells and alter the extracellular matrix. This leads to remodeling processes that obstruct the outflow of aqueous humor, thereby increasing intraocular pressure. Pronounced fluctuations in IOP as well as persistently elevated intraocular pressure further increase stress on the ganglion cells, thus promoting progressive neurodegeneration.

Schematic representation of the pathomechanisms in glaucoma. The graphic illustrates a top-to-bottom sequence, beginning with the disruption of the mitochondrial respiratory chain. This leads to an increase in free radicals and a loss of the antioxidant defense system, which in turn causes oxidative stress. Oxidative stress triggers inflammatory processes (neuroinflammation) and contributes to remodeling of the trabecular meshwork. As a result, intraocular pressure increases. In addition, oxidative stress directly leads to the death of retinal ganglion cells (neurodegeneration). A feedback loop shows that elevated intraocular pressure further amplifies oxidative stress, creating a vicious cycle.

3 therapeutic strategies of micronutrient supplementation

Bild Ophtaprotect® SEHNERV mit Schriftzügen "von Augenärzten entwickelt" und "3 Stategien zur Neuroprotektion"

To counteract neurodegeneration in glaucoma, various neuroprotective strategies are available, which should ideally be applied in combination:

I. Enhancement of the Mitochondrial Respiratory Chain

A central role is played by supporting energy production in the mitochondria. In particular, coenzyme Q10, an essential redox component of the electron transport chain in the mitochondrial membrane, exerts a decisive influence. Coenzyme Q10 also has antioxidant properties and stabilizes the cell membrane. Alpha-lipoic acid can also provide supportive effects. (R)-alpha-lipoic acid serves as a cofactor for mitochondrial enzymes such as pyruvate dehydrogenase and is therefore indispensable for cellular energy metabolism. Both substances contribute to strengthening cellular energy production and may thus protect retinal ganglion cells from functional loss.

II. Stabilization of the Mitochondrial and Cellular Membrane

Oxidative stress and neuroinflammation lead to damage of the mitochondrial and cellular membranes. This impairs membrane fluidity, selectivity, and structural integrity, thereby disrupting essential functions. However, the integrity of cell and mitochondrial membranes is crucial for the survival and function of neurons. During these damaging processes, membrane permeability increases, leading to loss of membrane potential and, subsequently, to the breakdown of membrane structures. The blood-brain barrier is also compromised. The resulting disturbances endanger cellular integrity in a lasting manner and are often difficult to reverse. Intact membranes are therefore not only vital for normal cell function but also for protection against further oxidative stress. As a fat-soluble antioxidant, vitamin E acts membrane-stabilizing and protects membrane lipids against peroxidation. A common approach to membrane stabilization is supplementation with citicoline, which is converted in the body, among other things, into phosphatidylcholine. Another approach is the direct supplementation with phosphatidylcholine (lecithin). Phosphatidylcholine stabilizes cellular and mitochondrial membranes, reduces oxidative stress, diminishes neuroinflammation, and protects against neuronal damage.

III. Reduction of Oxidative Stress

The reduction of oxidative stress is a central goal of neuroprotection. Antioxidants such as vitamin C, curcumin, coenzyme Q10, and alpha-lipoic acid are particularly noteworthy, as they neutralize free radicals and reduce damage caused by reactive oxygen species. This protects retinal ganglion cells, microglia, and trabecular meshwork cells from apoptosis. In addition, alpha-lipoic acid regenerates other antioxidants and promotes the synthesis of glutathione.
Explanatory graphic of all micronutrients in Ophtaprotect® SEHNERV and their effects on the mitochondrial respiratory chain, oxidative stress, and the cell membrane.

Did you know that healthcare professionals can receive free product samples of Ophtaprotect® SEHNERV upon request?

Expert Opinions and Publications”

Most glaucoma treatments focus on lowering intraocular pressure. However, this alone is often not sufficient to prevent progressive vision and visual field loss. To effectively counteract this neurodegeneration, new approaches are necessary.

DOG Symposium: Neurodegeneration in Glaucoma

DOG Symposium: Neurodegeneration in Glaucoma

All video contributions of the symposium (in German) can be found here:

  • Prof. Dr. med. Verena Prokosch
  • Prof. Dr. med. Stephanie Joachim
  • Prof. Dr. med. Carl Erb
  • Prof. Dr. Dr. Thomas Fuchsluger (moderation)

Current Neuroprotective Therapeutic Strategies

Prof. Dr. med. Carl Erb, a renowned glaucoma specialist, has been named one of Germany’s TOP physicians by FOCUS magazine for eight consecutive years. In 2019, he additionally received the distinction as a specialist in glaucoma (open-angle glaucoma). Since 2011, Prof. Erb has served as the leading glaucoma expert at the Klinik am Wittenberg Platz. Moreover, since 2010 he has been Vice President of the Glaucoma Section of the German Ophthalmological Society.

Focusing on more than just intraocular pressure

The exact cause of primary open-angle glaucoma has not yet been fully elucidated, but it is now understood to be a systemic neurodegenerative disease. Since lowering intraocular pressure cannot halt progression in all patients, complementary therapeutic approaches are being explored. Prof. Dr. Carl Erb highlights the importance of nutrition and lifestyle. You can read the full interview with Eyefox here.

Free Samples and Information Materials

Through the sample dispatch, ebiga-VISION aims to give you the opportunity to form your own impression, to provide your patients with comprehensive and straightforward advice, and to offer them an evidence-based option.

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How can patients obtain Ophtaprotect®SEHNERV?

Patients can obtain Ophtaprotect® SEHNERV in pharmacies or online from ebiga-VISION. If you would like to supply your patients directly through your practice shop, please contact us via the contact form. We will be happy to send you a PDF with our current prices and discount tiers. You can also easily reach us by phone to place an order. Tel (DE): +49 3834 838 12-12

An eye examination in progress: A male patient is seated at a slit lamp while a female optometrist or ophthalmologist performs the test, focusing on his eye health.

Evidence Base for Micronutrients – Results from Cell Culture, Animal Models, and Clinical Studies

“Patients need a paradigm shift – a multi-pronged strategy that not only focuses on controlling intraocular pressure, but also actively supports, protects, and even repairs ganglion cells and the optic nerve.”

G. O. Bou Ghanem

Findings from Cell Culture Studies

Schematische Darstellung einer Zellkultur
Alpha-lipoic acid
Alpha-lipoic acid improves the visual response properties of retinal ganglion cells after the induction of oxidative stress and counteracts neuronal loss5,6.
Curcumin
Curcumin reduces oxidative stress and protects retinal ganglion cells, microglia, and trabecular meshwork cells from apoptosis7–10.
Coenzym Q10
Coenzyme Q10 protects retinal ganglion cells from apoptosis11.

Findings from Animal Model Studies

Umrisse von 4 Mäusen als Symbol für die Evidenzbasis Klinische Studien
Curcumin
Curcumin reduces oxidative stress, modulates the NF-κB signaling pathway, and protects against the loss of retinal ganglion cells and microvessels8,10,12,13.
Alpha-lipoic acid
Alpha-lipoic acid reduces oxidative stress, enhances glutathione synthesis, and promotes the survival of retinal ganglion cells5,14–17.
Lecithin
Lecithin reduces oxidative stress, decreases microglial activation (neuroinflammation), and protects against neuronal damage18–20.
Coenzyme Q10
Coenzyme Q10 reduces oxidative stress, decreases mitochondrial neurotoxicity, and protects retinal ganglion cells from apoptosis11,21–23.
Vitamin E
Vitamin E lowers malondialdehyde levels and catalase activity, and protects the retina from damage20,24.
Vitamin C
Vitamin C improves the survival of retinal ganglion cells, the pattern electroretinogram, and visual acuity, and reduces intraocular pressure25.
B-Vitamins
B vitamins counteract retinal dysfunction and the loss of retinal ganglion cells26.

Findings from Clinical Studies

Umrisse von 5 Menschen als Symbol für die Evidenzbasis Klinische Studien
Sanz-González et al. (2020)
A 6-month supplementation with R-alpha-lipoic acid, taurine, vitamins C and E, lutein, zeaxanthin, zinc, copper, and docosahexaenoic acid counteracts oxidative stress in patients with primary open-angle glaucoma (POAG) and stabilizes morphological and functional parameters of the ocular surface (tear flow/dry eye).34
Rolle et al. (2020)
Treatment of POAG patients with a dietary supplement containing homotaurine, carnosine, forskolin, vitamins B1, B2 and B6, folic acid, and magnesium was able, after 2 to 6 months of daily intake, to slow the progression of functional damage (VF, IOP) and improve visual function (light sensitivity, contrast sensitivity).28
Harris et al. (2018)
One month of oral administration of an antioxidant preparation (vitamins C, E, B6, B12, folic acid, Mg, taurine, N-acetylcysteine, ALA, GBE, DHA, EPA, bilberry extract, coenzyme Q10, grape seed extract, quercetin) led to an increase in biomarkers of ocular blood flow in the retinal and retrobulbar vascular beds in patients with open-angle glaucoma.33
Mutolo et al. (2016)
A 12-month supplementation with forskolin, homotaurine, carnosine, folic acid, vitamins B1, B2, B6, and magnesium in patients with primary open-angle glaucoma (POAG) resulted in a reduction of IOP and an improvement in PERG amplitude after 6, 9, and 12 months, as well as improved foveal sensitivity after 12 months.27
Dolgova et al. (2013)
After a 3-month supplementation with lutein, zeaxanthin, β-carotene, bilberry extract, vitamins A, B2, C and E, copper, selenium, and zinc, patients with POAG and AMD showed a significant improvement in visual field, reaction time (p<0.05), and contrast sensitivity compared to baseline.32
Engin et al. (2007)
A 12-month supplementation with alpha-tocopherol (vitamin E) lowers the pulsatility index and resistance index of the ocular arteries as well as the posterior ciliary arteries, and reduces the differences in mean deviation (MD) of visual field testing in glaucoma patients.31
Cellini et al. (1998)
A 90-day supplementation with polyunsaturated fatty acids, docosahexaenoic acid, vitamin E, and B vitamins led to an improvement in visual field (MD, CPSD, SF) and contrast sensitivity in patients with glaucomatous optic neuropathy, compared to the group supplemented with B vitamins alone.30
Stark et al. (1985)
A 5-month treatment with pentoxifylline, nicotinic acid, and vitamins A and E led to a reduction or elimination of visual field defects in 114 glaucoma patients.29

Complete literature on the evidence base of the micronutrients in Ophtaprotect® SEHNERV

Download abstracts
  • 1Bou Ghanem, G. O., & Calkins, D. J. (2024, April 7). Neuroprotection: The Future of Glaucoma Treatment? The Ophthalmologist.
  • 2Bou Ghanem, G. O., Wareham, L. K., & Calkins, D. J. (2024). Addressing neurodegeneration in glaucoma: Mechanisms, challenges, and treatments. Progress in Retinal and Eye Research,100, 101261.
  • 3Erb, C. (2020). Sekundäre Neuroprotektion beim Glaukom durch ergänzende medikamentöse Therapiekonzepte. Klinische Monatsblätter Für Augenheilkunde, 237(02), 163–174.
  • 4Jünemann, A. G. M., Grieb, P., & Rejdak, R. (2021). Bedeutung von Citicolin bei der Glaukomerkrankung. Der Ophthalmologe, 118(5), 439–448.
  • 5Chidlow, G., Schmidt, K.-G., Wood, J. P. M., Melena, J., & Osborne, N. N. (2002). α-lipoic acid protects the retina against ischemia-reperfusion. Neuropharmacology, 43(6), 1015–1025.
  • 6 Xia, H., Nan, Y., Huang, X., Gao, J., & Pu, M. (2015). Effects of tauroursodeoxycholic acid and alpha-lipoic- acid on the visual response properties of cat retinal ganglion cells: An in vitro study. Investigative Ophthalmology and Visual Science, 56(11), 6638–6645.
  • 7 Matteucci, A., Frank, C., Domenici, M. R., Balduzzi, M., Paradisi, S., Carnovale-Scalzo, G., Scorcia, G., & Malchiodi-Albedi, F. (2005). Curcumin treatment protects rat retinal neurons against excitotoxicity: effect on N-methyl-D: -aspartate-induced intracellular Ca(2+) increase. Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale, 167(4), 641–648.
  • 8Yue, Y. K., Mo, B., Zhao, J., Yu, Y. J., Liu, L., Yue, C. L., & Liu, W. (2014). Neuroprotective effect of curcumin against oxidative damage in BV-2 microglia and high intraocular pressure animal model. Journal of Ocular Pharmacology and Therapeutics, 30(8), 657–664.
  • 9Lin, C., & Wu, X. (2016). Curcumin protects trabecular meshwork cells from oxidative stress. Investigative Ophthalmology and Visual Science, 57(10), 4327–4332.
  • 10 Davis, B. M., Pahlitzsch, M., Guo, L., Balendra, S., Shah, P., Ravindran, N., Malaguarnera, G., Sisa, C., Shamsher, E., Hamze, H., Noor, A., Sornsute, A., Somavarapu, S., & Cordeiro, M. F. (2018). Topical Curcumin Nanocarriers are Neuroprotective in Eye Disease. Scientific Reports, 8(1).
  • 11Lulli, M., Witort, E., Papucci, L., Torre, E., Schipani, C., Bergamini, C., Monte, M. D., & Capaccioli, S. (2012). Coenzyme Q10 instilled as eye drops on the cornea reaches the retina and protects retinal layers from apoptosis in a mouse model of kainate-induced retinal damage. Investigative Ophthalmology and Visual Science, 53(13), 8295–8302.
  • 12Burugula, B., Ganesh, B. S., & Chintala, S. K. (2011). Curcumin attenuates staurosporine-mediated death of retinal ganglion cells. Investigative Ophthalmology and Visual Science, 52(7), 4263–4273.
  • 13Wang, L., Li, C., Guo, H., Kern, T. S., Huang, K., & Zheng, L. (2011). Curcumin inhibits neuronal and vascular degeneration in retina after ischemia and reperfusion injury. PLoS ONE, 6(8).
  • 14Koriyama, Y., Nakayama, Y., Matsugo, S., & Kato, S. (2013). Protective effect of lipoic acid against oxidative stress is mediated by Keap1/Nrf2-dependent heme oxygenase-1 induction in the RGC-5 cellline. Brain Research, 1499, 145–157.
  • 15Ji, D., Majid, A. S. A., & Yin, Z. Q. (2013). α-Lipoic Acid Attenuates Light Insults to Neurones. Biological and Pharmaceutical Bulletin, 36(7), 1060–1067.
  • 16Wang, Y., Wang, W., Liu, J., Huang, X., Liu, R., Xia, H., Brecha, N. C., Pu, M., & Gao, J. (2016). Protective effect of ALA in crushed optic nerve cat retinal ganglion cells using a new marker RBPMS. PLoS ONE, 11(8).
  • 17Inman, D. M., Lambert, W. S., Calkins, D. J., & Horner, P. J. (2013). α-Lipoic Acid Antioxidant Treatment Limits Glaucoma-Related Retinal Ganglion Cell Death and Dysfunction. PLoS ONE, 8(6).
  • 18Kim, J. H., Choi, B. Y., Kho, A. R., Lee, S. H., Jeong, J. H., Hong, D. K., Lee, S. H., Sohn, M., Ryu, O. H., Choi, M. ‐G., & Suh, S. W. (2018). Acetylcholine precursor, citicoline (cytidine 5′‐diphosphocholine), reduces hypoglycaemia‐induced neuronal death in rats. Journal of Neuroendocrinology, 30(1).
  • 19 Kim, J. H., Lee, D. W., Choi, B. Y., Sohn, M., Lee, S. H., Choi, H. C., Ki Song, H., & Suh, S. W. (2015). Cytidine 5-diphosphocholine (CDP-choline) adversely effects on pilocarpine seizure-induced hippocampal neuronal death. Brain Research, 1595, 156–165.
  • 20 Aabdallah, D. M., & Eid, N. I. (2004). Possible neuroprotective effects of lecithin and α-tocopherol alone or in combination against ischemia/reperfusion insult in rat brain. Journal of Biochemical and Molecular Toxicology, 18(5), 273–278.
  • 21 Nakajima, Y., Inokuchi, Y., Nishi, M., Shimazawa, M., Otsubo, K., & Hara, H. (2008). Coenzyme Q10 protects retinal cells against oxidative stress in vitro and in vivo. Brain Research, 1226, 226–233.
  • 22Lee, D., Shim, M. S., Kim, K. Y., Noh, Y. H., Kim, H., Kim, S. Y., Weinreb, R. N., & Ju, W. K. (2014). Coenzyme Q10 inhibits glutamate excitotoxicity and oxidative stress-mediated mitochondrial alteration in a mouse model of glaucoma. Investigative Ophthalmology and Visual Science, 55(2), 993–1005.
  • 23Davis, B. M., Tian, K., Pahlitzsch, M., Brenton, J., Ravindran, N., Butt, G., Malaguarnera, G., Normando, E. M., Guo, L., & Cordeiro, M. F. (2017). Topical Coenzyme Q10 demonstrates mitochondrial-mediated neuroprotection in a rodent model of ocular hypertension. Mitochondrion, 36, 114–123.
  • 24Aydemir, O., Çelebi, S., Yılmaz, T., Yekeler, H., & Kükner, A. Ş. (2004). Protective Effects of Vitamin E Forms (Alpha-tocopherol, Gamma-tocopherol and d-alpha-tocopherol Polyethylene Glycol 1000 Succinate) on Retinal Edema During Ischemia–reperfusion Injury in the Guinea Pig Retina. International Ophthalmology, 25(5–6), 283–289.
  • 25Li, S., & Jakobs, T. C. (2023). Vitamin C protects retinal ganglion cells via SPP1 in glaucoma and after optic nerve damage. Life Science Alliance, 6(8).
  • 26Cammalleri, M., Monte, M. D., Amato, R., Bagnoli, P., & Rusciano, D. (2020). A dietary combination of forskolin with homotaurine, spearmint and B vitamins protects injured retinal ganglion cells in a rodent model of hypertensive glaucoma. Nutrients, 12(4).
  • 27 Mutolo, M. G., Albanese, G., Rusciano, D., & Pescosolido, N. (2016). Oral Administration of Forskolin, Homotaurine, Carnosine, and Folic Acid in Patients with Primary Open Angle Glaucoma: Changes in Intraocular Pressure, Pattern Electroretinogram Amplitude, and Foveal Sensitivity. Journal of Ocular Pharmacology and Therapeutics, 32(3), 178–183.
  • 28 Rolle, T., Dallorto, L., Rossatto, S., Curto, D., & Nuzzi, R. (2020). Assessing the Performance of Daily Intake of a Homotaurine, Carnosine, Forskolin, Vitamin B2, Vitamin B6, and Magnesium Based Food Supplement for the Maintenance of Visual Function in Patients with Primary Open Angle Glaucoma. Journal of Ophthalmology, 2020.
  • 29Stark, H. (1985). Untersuchungen mit dem computergesteuerten Perimeter Peritest über die Wirkung des Cosaldons A + E auf glaukomatöse Gesichtsfelddefekte. Ophthalmologica, 191(4), 238–249.
  • 30Cellini, M., Caramazza, N., Mangiafico, P., Possati, G. L., & Caramazza, R. (1998). Fatty acid use in glaucomatous optic neuropathy treatment. Acta Ophthalmologica Scandinavica, 76(S227), 41–42.
  • 31Engin, K. N., Engin, G., Kucuksahin, H., Oncu, M., Engin, G., & Guvener, B. (2007). Clinical Evaluation of the Neuroprotective Effect of α-Tocopherol against Glaucomatous Damage. European Journal of Ophthalmology, 17(4), 528–533.
  • 32Dolgova, I. G., Malishevskaia, T. N., Shatskikh, S. v, Lazareva, T. P., Ampilova, T. P., Nemtsova, I. v, Dorkina, I. L., Antipina, N. A., & Kalinina, O. N. (2013). [Efficacy of vitamin mineral complex “Focus forte” in combined treatment of primary open-angle glaucoma and age-related macular degeneration]. Vestnik Oftalmologii, 129(2), 74–78, 80.
  • 33Harris, A., Gross, J., Moore, N., Do, T., Huang, A., Gama, W., & Siesky, B. (2018). The effects of antioxidants on ocular blood flow in patients with glaucoma. Acta Ophthalmologica, 96(2), e237–e241.
  • 34Sanz-González, S. M., Raga-Cervera, J., Aguirre Lipperheide, M., Zanón-Moreno, V., Chiner, V., Ramírez, A. I., & Pinazo-Durán, M. D. (2020). Effect of an oral supplementation with a formula containing R-lipoic acid in glaucoma patients. Archivos de La Sociedad Española de Oftalmología (English Edition), 95(3), 120–129.