ROLE OF BDNF FOR THE TREATMENT OF GLAUCOMA AND RETINITIS PIGMENTOSA
*Luca Spaccapelo, MD
ABSTRACT
Primary open-angle glaucoma (POAG) is the most common form of glaucoma, representing up to 90% of cases. POAG is described as a multifactorial optic neuropathy that is chronic and progressive with a characteristic ac-quired loss of optic nerve fibres. The cause for the elevated is generally IOP accepted to be decreased facility of aqueous outflow through the trabecular meshwork. Retinitis pigmentosa (RP) is a group of relatively rare, inherited disorders characterized by progressive peripheral vision loss and night vision difficulties (nyctalopia) that can lead to central vision loss due to the degeneration of the rod photoreceptor cells in the retina. RP manifests initial symptoms independent of age; thus, RP diagnosis occurs anywhere from early infancy to late adulthood. Brain-derived neurotrophic factor (BDNF) is a 14 kDa protein belonging to the neurotrophin family of growth factors. BDNF has trophic functions in the hippocampus, cortex, and basal forebrain as well as the retina, motor neurons, the kidneys, saliva and the prostate. The notion that BDNF may have a role in treating the neurodegenerative aspects of POAG is underpinned by convincing preclinical evidence in animal models of glaucoma that BDNF administered intravitreously can, at least in part, rescue retinal ganglion cells (RGCs) under conditions such as those induced by increased intraocular pressure (IOP). Overall and despite a mechanistically sound rationale, the pharmacokinetic challenges indicate that instilled BDNF topical administration is associated with higher than normal risks, likely explaining the emphasis on alternative approaches (such as synthetic small molecule BDNF analogues or gene therapy approaches) in the last decade. Moreover, the high BDNF doses required to drive efficacy (and low target tissue penetration) also raise concerns over promotion of tumour growth resulting from BDNF taken up from non-retinal tissues. In conclusion, even if preliminary evidences are available, further studies are necessary in order to clarify the role of BDNF for the treatment of glaucoma and retinitis pigmentosa.
Keywords: Brain-derived neurotrophic factor, Glaucoma, Retinitis Pigmentosa, increased intraocular pressure, Neurotrophins.
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