The Key Role of Brain-Derived Neurotrophic Factor (BDNF) in Pathophysiology of Glaucoma and Its Therapeutic Potential

Brain-Derived Neurotrophic Factor (BDNF) in Pathophysiology of Glaucoma

Authors

  • Muhammad Usman Durrani Department of Ophthalmology, Pakistan Navy Station, Shifa Hospital, Karachi, Pakistan
  • Anum Usman Department of Histopathology, Al Nafees Medical College and Hospital Isra University, Islamabad, Pakistan
  • Fakhra Noureen Department of Pathology, Akhtar Saeed Medical College, Rawalpindi, Pakistan
  • Abdul Munim Department of Ophthalmology, Peshawar Medical College, Peshawar, Pakistan
  • Sohaib Abbas Department of Ophthalmology, Kind Edward Medical University Mayo Hospital, Lahore, Pakistan
  • Zain ul Abden Bilal Ahmed Department of Ophthalmology, Liaquat Institute of Medical and Health Science, Thatta, Pakistan
  • Muhammad Haseeb Khaliq Department of Pathology, University of Health Sciences, Lahore, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v5i10.2267

Keywords:

Brain-derived Neurotrophic Factor, Glaucoma, Neuroprotection, Retinal Ganglion Cells

Abstract

Glaucoma, a leading cause of irreversible blindness, is increasingly recognized as a neurodegenerative disease affecting broader neuro-ophthalmic pathways. Brain-derived neurotrophic Factor is a crucial neurotrophin, that supports the growth, maintenance, and survival of neurons and has been implicated in glaucomatous damage where its levels are diminished. Objectives: To focus on the role of Brain-Derived Neurotrophic Factor in the pathophysiology of glaucoma and its therapeutic potential by enhancing the survival of retinal ganglion cells. Methods: The studies in this review are taken from well-known public libraries for scientific research such as PubMed (60%), Science Direct (25%) and Springer Link (15%), in line with PRISMA guidelines. Various works conducted over the past decade from different parts of the world, including North America, Europe, and Asia, have provided evidence that the augmentation of Brain-Derived Neurotrophic Factor signalling may be a very effective approach to managing or halting the progression of glaucomatous optic neuropathy through neuroprotection and improving retinal ganglion cells survival. Results: Studies in both animals and humans indicate that Brain-Derived Neurotrophic Factor and its downstream signals promote the survival of retinal ganglion cells and decrease the extent of apoptotic cell death, oxidative stress, and inflammation in glaucoma. Moreover, enhancements of Brain-Derived Neurotrophic Factor neuroprotective effects are supported by factors such as Nerve growth factor and Brain-Derived Neurotrophic Factor. Conclusion: It was concluded that Brain-derived neurotrophic Factor has the potential to be used as a diagnostic marker for Glaucoma as well as it could be evaluated for its therapeutic potential against the disease.  

References

Wu Y, Hu Y, Jiang N, Anantharanjit R, Yetisen AK, Cordeiro MF. Quantitative Brain-Derived Neurotrophic Factor Lateral Flow Assay for Point-Of-Care Detection of Glaucoma. Lab on a Chip. 2022; 22(18): 3521-32. doi: 10.1039/D2LC00431C.

Osborne A, Khatib TZ, Songra L, Barber AC, Hall K, Kong GY et al. Neuroprotection of Retinal Ganglion Cells by A Novel Gene Therapy Construct That Achieves Sustained Enhancement of Brain-Derived Neurotrophic Factor/Tropomyosin-Related Kinase Receptor-B Signalling. Cell Death & Disease. 2018 Sep; 9(10): 1007. doi: 10.1038/s41419-018-1041-8.

Fathy M, Darweesh AM, Sharaf S, El-Hanafi HM, Ghaleb FM, Fahmy IA et al. Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism in A Cohort of Egyptian Primary Open-Angle Glaucoma (POAG) Patients. Bulletin of the National Research Centre. 2020 Dec; 44: 1-7. doi: 10.1186/s42269-020-00288-x.

Wormald R, Virgili G, Azuara-Blanco A. Systematic Reviews and Randomised Controlled Trials On Open Angle Glaucoma. Eye. 2020 Jan; 34(1): 161-7. doi: 10.1038/s41433-019-0687-5.

Amin N, Xie S, Tan X, Chen Y, Ren Q, Botchway BO et al. Optimized Integration of Fluoxetine and 7, 8-Dihydroxyflavone as an Efficient Therapy for Reversing Depressive-Like Behavior in Mice During the Perimenopausal Period. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2020 Jul; 101: 109939. doi: 10.1016/j.pnpbp.2020.109939.

Boia R, Ruzafa N, Aires ID, Pereiro X, Ambrósio AF, Vecino E et al. Neuroprotective Strategies for Retinal Ganglion Cell Degeneration: Current Status and Challenges Ahead. International Journal of Molecular Sciences. 2020 Mar; 21(7): 2262. doi: 10.3390/ijms21072262.

Huang P, Liu A, Song Y, Hope JM, Cui B, Duan L. Optical Activation of Trkb Signaling. Journal of Molecular Biology. 2020 Jun; 432(13): 3761-70. doi: 10.1016/j.jmb.2020.05.002.

Shen T, Gupta VK, Klistorner A, Chitranshi N, Graham SL, You Y. Sex-Specific Effect of BDNF Val66Met Genotypes On the Progression of Open-Angle Glaucoma. Investigative Ophthalmology & Visual Science. 2019 Mar; 60(4): 1069-75. doi: 10.1167/iovs.18-26364.

Saccà SC, Paluan F, Gandolfi S, Manni G, Cutolo CA, Izzotti A. Common Aspects Between Glaucoma and Brain Neurodegeneration. Mutation Research/Reviews in Mutation Research. 2020 Oct; 786: 108323. doi: 10.1016/j.mrrev.2020.108323.

Johnson TV, Bull ND, Martin KR. Neurotrophic Factor Delivery as A Protective Treatment for Glaucoma. Experimental Eye Research. 2011 Aug; 93(2): 196-203. doi: 10.1016/j.exer.2010.05.016.

Basavarajappa D, Galindo-Romero C, Gupta V, Agudo-Barriuso M, Gupta VB, Graham SL et al. Signalling Pathways and Cell Death Mechanisms in Glaucoma: Insights into the Molecular Pathophysiology. Molecular Aspects of Medicine. 2023 Dec; 94: 101216. doi: 10.1016/j.mam.2023.101216.

Liang Y, Yu YH, Yu HJ, Ma LS. Effect of BDNF-TrKB Pathway On Apoptosis of Retinal Ganglion Cells in Glaucomatous Animal Model. European Review for Medical & Pharmacological Sciences. 2019 May; 23(9).

Chiha W, Bartlett CA, Petratos S, Fitzgerald M, Harvey AR. Intravitreal Application of AAV-BDNF or Mutant AAV-CRMP2 Protects Retinal Ganglion Cells and Stabilizes Axons and Myelin After Partial Optic Nerve Injury. Experimental Neurology. 2020 Apr; 326: 113167. doi: 10.1016/j.expneurol.2019.113167.

Mallone F, Sacchetti M, Bruscolini A, Scuderi L, Marenco M, Lambiase A. Neurotrophic Factors in Glaucoma and Innovative Delivery Systems. Applied Sciences. 2020 Dec; 10(24): 9015. doi: 10.3390/app10249015.

Park HY, Kim SW, Kim JH, Park CK. Increased Levels of Synaptic Proteins Involved in Synaptic Plasticity After Chronic Intraocular Pressure Elevation and Modulation by Brain-Derived Neurotrophic Factor in A Glaucoma Animal Model. Disease models & mechanisms. 2019 Jun; 12(6): dmm037184. doi: 10.1242/dmm.037184.

Gupta V, You Y, Li J, Gupta V, Golzan M, Klistorner A, van den Buuse M, Graham S. BDNF impairment is associated with age-related changes in the inner retina and exacerbates experimental glaucoma. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2014 Sep 1;1842(9):1567-78.

Lambuk L, Mohd Lazaldin MA, Ahmad S, Iezhitsa I, Agarwal R, Uskoković V et al. Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in Glaucoma: A Review of Current State of the Art. Frontiers in Pharmacology. 2022 May; 13: 875662. doi: 10.3389/fphar.2022.875662.

Chen Y, Yang X, Mao J. The Neuroprotective Effect of Activation of Sigma-1 Receptor on Neural Injury by Optic Nerve Crush. Investigative Ophthalmology and Visual Science. 2023 Sep; 64(12): 9-. doi: 10.1167/iovs.64.12.9.

Claes M, De Groef L, Moons L. Target-Derived Neurotrophic Factor Deprivation Puts Retinal Ganglion Cells On Death Row: Cold Hard Evidence and Caveats. International Journal of Molecular Sciences. 2019 Sep; 20(17): 4314. doi: 10.3390/ijms20174314.

Wójcik-Gryciuk A, Gajewska-Woźniak O, Kordecka K, Boguszewski PM, Waleszczyk W, Skup M. Neuroprotection of Retinal Ganglion Cells with AAV2-BDNF Pretreatment Restoring Normal Trkb Receptor Protein Levels in Glaucoma. International Journal of Molecular Sciences. 2020 Aug; 21(17): 6262. doi: 10.3390/ijms21176262.

Lazaldin MA, Iezhitsa I, Agarwal R, Agarwal P, Ismail NM. Neuroprotective Effects of Exogenous Brain-Derived Neurotrophic Factor On Amyloid-Beta 1–40-Induced Retinal Degeneration. Neural Regeneration Research. 2023 Feb; 18(2): 382-8. doi: 10.4103/1673-5374.346546.

Arranz-Romera A, Hernandez M, Checa-Casalengua P, Garcia-Layana A, Molina-Martinez IT, Recalde S et al. A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies. Pharmaceuticals. 2021 Jan; 14(1): 50. doi: 10.3390/ph14010050.

Lazzara F, Amato R, Platania CB, Conti F, Chou TH, Porciatti V et al. 1α, 25-dihydroxyvitamin D 3 Protects Retinal Ganglion Cells in Glaucomatous Mice. Journal of Neuro Inflammation. 2021 Dec; 18: 1-9. doi: 10.1186/s12974-021-02263-3.

Oddone F, Roberti G, Micera A, Busanello A, Bonini S, Quaranta L et al. Exploring Serum Levels of Brain Derived Neurotrophic Factor and Nerve Growth Factor Across Glaucoma Stages. PLoS One. 2017 Jan; 12(1): e0168565. doi: 10.1371/journal.pone.0168565.

Igarashi T, Nakamoto K, Kobayashi M, Suzuki H, Tobita Y, Igarashi T et al. Serum Brain-Derived Neurotrophic Factor in Glaucoma Patients in Japan: An Observational Study. Journal of Nippon Medical School. 2020 Dec; 87(6): 339-45. doi: 10.1272/jnms.JNMS.2020_87-605.

Igarashi T, Nakamoto K, Kobayashi M, Suzuki H, Arima T, Tobita Y et al. Brain-derived neurotrophic factor in the aqueous humor of glaucoma patients. Journal of Nippon Medical School. 2021 Apr; 88(2): 128-32. doi: 10.1272/jnms.JNMS.2021_88-305.

Wu Y, Zhang Y, Hu Y, Jiang N, Patel RP, Yetisen AK et al. Fluorescent Quantum Dots Based Lateral Flow Assay for Rapid Quantitative Detection of Ciliary Neurotrophic Factor in Glaucoma. Advanced Materials Technologies. 2024 Aug; 9(6): 2400238. doi: 10.1002/admt.202400238.

Dekeyster E, Geeraerts E, Buyens T, Van den Haute C, Baekelandt V, De Groef L et al. Tackling Glaucoma from Within The Brain: An Unfortunate Interplay of BDNF and TrkB. PLoS One. 2015 Nov; 10(11): e0142067. doi: 10.1371/journal.pone.0142067.

Fathy M, Darweesh AM, Sharaf S, Ghaleb FM, Fahmy IA, Hussein SM. Assessment of Brain-derived Neurotrophic Factor (BDNF) Gene Polymorphism in a Patients with Cohort of Egyptian Primary Open-Angle Glaucoma (POAG). In: Current Overview on Science and Technology Research. 2022; 2: 1-11. doi: 10.9734/bpi/costr/v2/2212B.

Bhartiya S, Dhingra D, Ichhpujani P. Is it time for Precision Medicine in Glaucoma? CLEVER Clinical and Experimental Vision and Eye Research. 2020 Jul; 3(2): 4-12. doi: 10.15713/ins.clever.49

Liu C, Chan CB, Ye K. 7, 8-Dihydroxyflavone, A Small Molecular Trkb Agonist, is Useful for Treating Various BDNF-Implicated Human Disorders. Translational Neurodegeneration. 2016 Dec; 5: 1-9. doi: 10.1186/s40035-015-0048-7.

Hakim A, Guido B, Narsineni L, Chen DW, Foldvari M. Gene Therapy Strategies for Glaucoma from IOP Reduction to Retinal Neuroprotection: Progress Towards Non-Viral Systems. Advanced Drug Delivery Reviews. 2023 May; 196: 114781. doi: 10.1016/j.addr.2023.114781.

Song W, Huang P, Zhang C. Neuroprotective Therapies for Glaucoma. Drug Design, Development and Therapy. 2015 Mar; 9: 1469-79. doi: 10.2147/DDDT.S80594.

Danesh-Meyer HV, Levin LA. Glaucoma as a Neurodegenerative Disease. Journal of Neuro-Ophthalmology. 2015 Sep; 35: S22-8. doi: 10.1097/WNO.0000000000000293.

Omaka AU, Ezeigbo A. New Trends in Neuro-protection in Glaucoma. Journal of the Nigerian Optometric Association. 2024 Jul; 26(1): 48-58. doi: 10.4314/jnoa.v26i1.7.

Afarid M, Torabi-Nami M, Zare B. Neuroprotective and Restorative Effects of the Brain-Derived Neurotrophic Factor in Retinal Diseases. Journal of the Neurological Sciences. 2016 Apr; 363: 43-50. doi: 10.1016/j.jns.2016.02.024.

Jindal V. Glaucoma: An Extension of Various Chronic Neurodegenerative Disorders. Molecular Neurobiology. 2013 Aug; 48: 186-9. doi: 10.1007/s12035-013-8416-8.

Wareham LK, Risner ML, Calkins DJ. Protect, Repair, and Regenerate: Towards Restoring Vision in Glaucoma. Current Ophthalmology Reports. 2020 Dec; 8: 301-10. doi: 10.1007/s40135-020-00259-5.

Vergroesen JE, De Crom TO, Van Duijn CM, Voortman T, Klaver CC, Ramdas WD. MIND Diet Lowers Risk of Open-Angle Glaucoma: The Rotterdam Study. European Journal of Nutrition. 2023 Feb; 62(1): 477-87. doi: 10.1007/s00394-022-03003-w.

Fudalej E, Justyniarska M, Kasarełło K, Dziedziak J, Szaflik JP, Cudnoch-Jędrzejewska A. Neuroprotective Factors of the Retina and Their Role in Promoting Survival of Retinal Ganglion Cells: A Review. Ophthalmic Research. 2021 Jun; 64(3): 345-55. doi: 10.1159/000514441

Rhee J, Shih KC. Use of Gene Therapy in Retinal Ganglion Cell Neuroprotection: Current Concepts and Future Directions. Biomolecules. 2021 Apr; 11(4): 581. doi: 10.3390/biom11040581.

Naik S, Pandey A, Lewis SA, Rao BS, Mutalik S. Neuroprotection: A Versatile Approach to Combat Glaucoma. European Journal of Pharmacology. 2020 Aug; 881: 173208. doi: 10.1016/j.ejphar.2020.173208.

Downloads

Published

2024-10-31
CITATION
DOI: 10.54393/pjhs.v5i10.2267
Published: 2024-10-31

How to Cite

Durrani, M. U., Usman, A., Noureen, F., Munim, A., Abbas, S., Bilal Ahmed, Z. ul A., & Khaliq, M. H. (2024). The Key Role of Brain-Derived Neurotrophic Factor (BDNF) in Pathophysiology of Glaucoma and Its Therapeutic Potential: Brain-Derived Neurotrophic Factor (BDNF) in Pathophysiology of Glaucoma . Pakistan Journal of Health Sciences, 5(10), 240–247. https://doi.org/10.54393/pjhs.v5i10.2267

Issue

Section

Systematic Review

Plaudit