• THE RELATIONSHIP BETWWEN BDNF GENE THERAPY AND GLAUCOMA BLINDNESS
  • mobina movahed majd,1,* danyal farajnia rick,2 zhila shokrian,3 nahid shokrian,4
    1. Student of research Committe, Medical University of Sarab
    2. Student of research Committe, Medical University of Sarab
    3. Student of research Committe, Medical University of Sarab
    4. Member Midwifery Scientific Association of Iran


  • Introduction: Brain-derived neurotrophic factor (BDNF) is a predominant neurotrophic factor in the brain that plays an important role in the mechanisms of differentiation, regeneration, and plasticity. BDNF inhibits ischemia-induced neuronal death, oxidative stress, glutamate toxicity, and proteins such as amyloid B. Glaucoma is the second most common cause of blindness, affecting 70 to 80 million people worldwide. The death of retinal ganglion cells (RGC) is the main cause of blindness associated with this disease. A new opportunity for glaucoma treatment is the use of technologies related to stem cells and gene therapy. Previous studies have shown that intravitreal delivery of brain-derived neurotrophic factor (BDNF), by injection of recombinant protein or by gene therapy can reduce retinal ganglion cell (RGC) loss after optic nerve injury. BDNF gene therapy. It can improve RGC survival in experimental models of glaucoma, which is the leading cause of irreversible blindness worldwide. Increased concentrations of neurotrophic factors in ganglion cells to prevent cell death were seen in glaucoma.
  • Methods: In this article, the relationship between BDNF gene therapy and glaucoma has been investigated. The articles from 2015 to 2022 have been reviewed from PubMed and science direct databases.
  • Results: Glaucoma is the leading cause of irreversible blindness worldwide and is characterized by progressive and permanent damage to the optic nerve, leading to the loss of retinal ganglion cells (RGC). BDNF levels in the serum of patients with POAG and tears of normotensive glaucoma patients are significantly lower than those of controls, suggesting that BDNF may be a biomarker for glaucoma. BDNF gene expression in the retina promotes robust RGC survival in various experimental glaucoma models, including optic nerve transaction and elevated IOP. Overexpression of the BDNF receptor TrkB in RGCs can stimulate RGC survival after optic nerve transfection. These findings suggest that BDNF-TrkB signaling is another good therapeutic target for glaucoma.
  • Conclusion: Several studies have shown that intravitreal delivery of BDNF by recombinant protein injection or through gene therapy methods can reduce RGC loss after optic nerve injury. BDNF is produced from a precursor protein called pre-pro-BDNF, which is cleaved into proBDNF. After that, pro-BDNF is cleaved to mature BDNF. TrkB begins to dimerize upon binding to mature BDNF. This cascade activates the signaling in the target cell with at least three different transmission pathways to maintain the survival, growth, and synaptic and plasticity of neurons. TrkB activation is a potential therapy for glaucoma relief. Considering the role of BDNF in three signaling pathways that lead to neural growth, survival, and plasticity, it seems that BDNF is the most important substance in maintaining neural health in the brain. Scientists have accumulated a large amount of information about the biology of BDNF-TrkB and the role of BDNF in synaptic plasticity and synaptic growth. In addition, BDNF is known to be a neuroprotective agent that can repair synaptic defects.
  • Keywords: GENE THERAPY,BDNF,RGC,SIGNALING PATHWAY