Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

Igor Khalin,1 Renad Alyautdin,2 Ganna Kocherga,3 Muhamad Abu Bakar1 1Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia; 2Scientific Centre for Expertise of Medical Application Products, Moscow, Russia; 3Ophthalmic Microsurgery Department, International Medical Center Oftalmika, Kharkiv, UkraineAbstract: Neurodegenerative causes of blindness and deafness possess a major challenge in their clinical management as proper treatment guidelines have not yet been found. Brain-derived neurotrophic factor (BDNF) has been established as a promising therapy against neurodegenerative disorders including hearing and visual loss. Unfortunately, the blood–retinal barrier and blood–cochlear barrier, which have a comparable structure to the blood–brain barrier prevent molecules of larger sizes (such as BDNF) from exiting the circulation and reaching the targeted cells. Anatomical features of the eye and ear allow use of local administration, bypassing histo-hematic barriers. This paper focuses on highlighting a variety of strategies proposed for the local administration of the BDNF, like direct delivery, viral gene therapy, and cell-based therapy, which have been shown to successfully improve development, survival, and function of spiral and retinal ganglion cells. The similarities and controversies for BDNF treatment of posterior eye diseases and inner ear diseases have been analyzed and compared. In this review, we also focus on the possibility of translation of this knowledge into clinical practice. And finally, we suggest that using nanoparticulate drug-delivery systems may substantially contribute to the development of clinically viable techniques for BDNF delivery into the cochlea or posterior eye segment, which, ultimately, can lead to a long-term or permanent rescue of auditory and optic neurons from degeneration. Keywords: brain-derived neurotrophic factor, neurodegeneration, posterior eye segment, inner ear, targeted drug-delivery, nanoparticle