Salvage of the retinal ganglion cells in transition phase in Alzheimer’s disease with topical coenzyme Q10: is it possible?

  • Refika Hande KarakahyaEmail author
  • Tuba Şaziye Özcan



The evaluation of the short-term effect of topically applied coenzyme Q10 (CoQ10) on retina and choroid in Alzheimer’s disease (AD) was aimed in this study.


Randomized controlled study included a total of 93 patients, 62 of whom with AD. Thirty (32.3%) AD patients received treatment (Group 1), 32 (34.4%) AD patients observed without treatment (Group 2), and Group 3 included 31 (33.3%) healthy controls (HC). Neurological and ophthalmological examinations including optical coherence tomography (OCT) were executed.


Retinal nerve fiber layer (RNFL) thickness in all quadrants increased following CoQ10 treatment in Group 1; however significant rise yielded in average and temporal quadrant RNFL thickness. Average and superonasal sector ganglion cell-inner plexiform layer (GCIPL) thickness increased significantly following CoQ10 treatment. The correlation analysis between difference in pre- and posttreatment OCT values in Group 1 revealed that rise in average RNFL thickness was inversely correlated with duration of the disease and rise in average GCIPL thickness and superonasal sector thickness was inversely correlated with severity of the disease.


Short-term topical CoQ10 resulted in improvement in AD related retinal ganglion cell (RGC) loss which may reflect the salvage of some RGCs in the reversible transitional phase. More bioavailability through intravitreal route of administration and longer duration of effect with sustained release forms may possibly help enhalting the RGC loss, especially incipience of neurodegenerative diseases.


Alzheimer’s disease Coenzyme Q10 Neurodegeneration Optical coherence tomography 


Author contributions

Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work: Refika Hande Karakahya, Tuba Şaziye Özcan

Drafting the work or revising it critically for important intellectual content: Tuba Şaziye Özcan

Final approval of the version to be published: Refika Hande Karakahya, Tuba Şaziye Özcan

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict(s) of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ordu University Ethical Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Statement of informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M et al (2005) Alzheimer's disease international. Global prevalence of dementia: a Delphi consensus study. Lancet 366:2112–2117CrossRefGoogle Scholar
  2. 2.
    Perl DP (2010) Neuropathology of Alzheimer’s disease. Mt Sinai J Med 77:32–42CrossRefGoogle Scholar
  3. 3.
    Jack CR, Albert MS, Knopman DS, McKhann GM, Sperling RA, Carrillo MC et al (2011) Introduction to the recommendations from the national institute on aging-Alzheimer’s association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement J Alzheimer’s Assoc 7:257–262CrossRefGoogle Scholar
  4. 4.
    McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH (2011) The diagnosis of dementia due to Alzheimer's disease: recommendations from the national institute on aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7:263–269CrossRefGoogle Scholar
  5. 5.
    Cronin-Golomb A, Corkin S, Rizzo JF, Cohen J, Growdon JH, Banks KS (1991) Visual dysfunction in Alzheimer’s disease: relation to normal aging. Ann Neurol 29:41–52CrossRefGoogle Scholar
  6. 6.
    Hinton DR, Sadun AA, Blanks JC, Miller CA (1986) Optic nerve degeneration in Alzheimer’s disease. N Engl J Med 315:485–487CrossRefGoogle Scholar
  7. 7.
    La Morgia C, Ross-Cisneros FN, Koronyo Y, Hannibal J, Gallassi R, Cantalupo G et al (2016) Melanopsin retinal ganglion cell loss in Alzheimer disease. Ann Neurol 79:90–109CrossRefGoogle Scholar
  8. 8.
    Berisha F, Feke GT, Trempe CL, McMeel JW, Schepens CL (2007) Retinal abnormalities in early Alzheimer's disease. Invest Ophthalmol Vis Sci 48:2285–2289CrossRefGoogle Scholar
  9. 9.
    Kalaria RN (2000) The role of cerebral ischemia in Alzheimer’s disease neurobiology of aging. Neurobiol Aging 21:321–330CrossRefGoogle Scholar
  10. 10.
    Bulut M, Yaman A, Erol MK, Kurtuluş F, Toslak D, Doğan B (2016) Choroidal thickness in patients with mild cognitive impairment and Alzheimer's type dementia. J Ophthalmol. Scholar
  11. 11.
    Cunha JP, Proença R, Dias-Santos A, Melancia D, Almeida R, Águas H et al (2017) Choroidal thinning: Alzheimer's disease and aging. Alzheimers Dement 30:11–17Google Scholar
  12. 12.
    Wang X, Wang W, Li L, Perry G, Lee HG, Zhu X (2014) Oxidative stress and mitochondrial dysfunction in Alzheimer's disease. Biochim Biophys Acta 1842:1240–1247CrossRefGoogle Scholar
  13. 13.
    Lee J, Boo JH, Ryu H (2009) The failure of mitochondria leads to neurodegeneration: do mitochondria need a jump start? Adv Drug Deliv Rev 61:1316–1323CrossRefGoogle Scholar
  14. 14.
    McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology 34:939–944CrossRefGoogle Scholar
  15. 15.
    He XF, Liu YT, Peng C, Zhang F, Zhuang S, Zhang JS (2012) Optical coherence tomography assessed retinal nerve fiber layer thickness in patients with Alzheimer’s disease: a meta-analysis. Int J Ophthalmol 5:401–405PubMedPubMedCentralGoogle Scholar
  16. 16.
    den Haan J, Verbraak FD, Visser PJ, Bouwman FH (2017) Retinal thickness in Alzheimer’s disease: a systematic review and meta-analysis. Alzheimers Dement 6:162–170Google Scholar
  17. 17.
    Iseri PK, Altinas O, Tokay T, Yuksel N (2006) Relationship between cognitive impairment and retinal morphological and visual functional abnormalities in Alzheimer disease. J Neuroophthalmol 26:18–24CrossRefGoogle Scholar
  18. 18.
    Cunha LP, Lopes LC, Costa-Cunha LV, Costa CF, Pires LA, Almeida AL et al (2016) Macular thickness measurements with frequency domain-OCT for quantification of retinal neural loss and its correlation with cognitive impairment in Alzheimer’s disease. PLoS One. CrossRefGoogle Scholar
  19. 19.
    Kromer R, Serbecic N, Hausner L, Froelich L, Aboul-Enein F, Beutelspacher SC (2014) Detection of retinal nerve fiber layer defects in Alzheimer’s disease using SD-OCT. Front Psychiatry 5:22CrossRefGoogle Scholar
  20. 20.
    Kirbas S, Turkyilmaz K, Anlar O, Tufekci A, Durmus M (2013) Retinal nerve fiber layer thickness in patients with Alzheimer disease. J Neuroophthalmol 33:58–61CrossRefGoogle Scholar
  21. 21.
    Oktem EO, Derle E, Kibaroglu S, Oktem C, Akkoyun I, Can U (2015) The relationship between the degree of cognitive impairment and retinal nerve fiber layer thickness. Neurol Sci 36:1141–1146CrossRefGoogle Scholar
  22. 22.
    Cunha JP, Moura-Coelho N, Proença RP, Dias-Santos A, Ferreira J, Louro C et al (2016) Alzheimer’s disease: a review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo. Graefes Arch Clin Exp Ophthalmol 254:2079–2092CrossRefGoogle Scholar
  23. 23.
    Cunha LP, Almeida AL, Costa-Cunha LV, Costa CF, Monteiro ML (2016) The role of optical coherence tomography in Alzheimer’s disease. Int J Retina Vitreous 2:24CrossRefGoogle Scholar
  24. 24.
    Cheung CY, Ong YT, Hilal S, Ikram MK, Low S, Ong YL et al (2015) Retinal ganglion cell analysis using high-definition optical coherence tomography in patients with mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 45:45–56CrossRefGoogle Scholar
  25. 25.
    Martin EG, Bambo MP, Marquesetal ML (2016) Ganglion cell layer measurements correlate with disease severity in patients with Alzheimer’s disease. Acta Ophthalmol 94:454–459CrossRefGoogle Scholar
  26. 26.
    Williams MA, Mcgowan AJ, Cardwell CR, Cheung CY, Craig D, Passmore P (2015) Retinal microvascular network attenuation in Alzheimer's disease. Alzheimers Dement 1:229–235Google Scholar
  27. 27.
    Tzekov R, Mullan M (2014) Vision function abnormalities in Alzheimer disease. Surv Ophthalmol 59:414–433CrossRefGoogle Scholar
  28. 28.
    Ajith TA (2013) Mitochondria: oxidative stress, dysfunction and cell death. VNT Biol Med Chem 1:21–32Google Scholar
  29. 29.
    Dumont M, Kipiani K, Yu F, Wille E, Katz M, Calingasan NY et al (2011) Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis 27:211–223CrossRefGoogle Scholar
  30. 30.
    Ishrat T, Khan MB, Hoda MN, Yousuf S, Ahmad M, Ansari MA et al (2006) Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behav Brain Res 171:9–16CrossRefGoogle Scholar
  31. 31.
    Qu J, Kaufman Y, Washington I (2009) Coenzyme q10 in the human retina. Invest Ophthalmol Vis Sci 50:1814–1818CrossRefGoogle Scholar
  32. 32.
    Durán-Prado M, Frontiñán J, Santiago-Mora R, Peinado JR, Parrado-Fernández C, Gómez-Almagro MV et al (2014) Coenzyme Q10 protects human endothelial cells from β-amyloid uptake and oxidative stress-induced injury. PLoS One. CrossRefGoogle Scholar
  33. 33.
    Feher J, Kovacs B, Kovacs I, Schveoller M, Papale A, Balacco Gabrieli C (2015) Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-l-carnitine, n-3 fatty acids, and coenzyme Q10. Int J Ophthalmol 219:154–166Google Scholar
  34. 34.
    Paris V, Centofanti M, Gandolfi S, Marangoni D, Rossetti L, Tanga L et al (2014) Effects of coenzyme Q10 in conjunction with vitamin E on retinal-evoked and cortical-evoked responses in patients with open-angle glaucoma. J Glaucoma 23:391–404CrossRefGoogle Scholar
  35. 35.
    Fato R, Bergamini C, Leoni S, Pinna A, Carta F, Cardascia N et al (2010) Coenzyme Q10 vitreous levels after administration of coenzyme Q10 eyedrops in patients undergoing vitrectomy. Acta Ophthalmol.
  36. 36.
    Porciatti V, Ventura LM (2012) Retinal ganglion cell functional plasticity and optic neuropathy: a comprehensive model. J Neuroophthalmol 32:354–358CrossRefGoogle Scholar
  37. 37.
    Banitt MR, Ventura LM, Feuer WJ, Savatovsky E, Luna G, Shif O et al (2013) Progressive loss of retinal ganglion cell function precedes structural loss by several years in glaucoma suspects. Invest Ophthalmol Vis Sci.

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of OphthalmologyOrdu University School of MedicineOrduTurkey
  2. 2.Department of NeurologyOrdu University School of MedicineOrduTurkey

Personalised recommendations