Brain‐derived neurotrophic factor alleviates clinical symptoms of experimental autoimmune uveoretinitis and supports retinal regeneration

Abstract

Purpose: Brain‐derived neurotrophic factor (BDNF) is one of the most important neurotrophins that has a fundamental role in the regulation of neuronal growth, proliferation, and regeneration, as well as an important modulatory effect on the immune cells. In addition, BDNF potentiates the neurodifferentiation of Müller cells (MCs), thus supporting retinal regeneration. Therefore, we aimed to investigate the anti‐inflammatory effect of BDNF in experimental autoimmune uveoretinitis (EAU), a severe neuroinflammatory condition, and whether BDNF could facilitate the regenerative capacity of MCs in EAU.Methods: EAU in mice was induced by s.c. administration of retinal antigen IRBP1‐20 emulsified in a complete Freud's adjuvant, followed by i.v. administration of Pertussis toxin. BDNF was administered daily in the form of eye drops from day 8 to day 14 after immunization. On day 14, fundoscopy was performed to assess clinical signs of EAU. Mice were then euthanized, and their eyes and retinas were isolated for further Western blot, RT‐qPCR, flow cytometry, and immunohistochemistry analyses.Results: The treatment with BDNF significantly improved the clinical manifestations of EAU, including optic disc oedema, vasculitis, and inflammatory infiltrates in the retina. BDNF significantly decreased the infiltration of CD4+ T cells, CD8+ T cells, and CD11b+ myeloid cells into the retina and also suppressed the expression of several pro‐inflammatory cytokines and chemokines. In addition, BDNF administration significantly increased the expression of markers of neurogenesis in retinal MCs.Conclusions: Together, our results demonstrate that BDNF has important anti‐inflammatory and neurogenic properties and that it may serve as a promising target for developing novel therapeutic strategies for neurodegenerative and neuroinflammatory diseases of the retina.Support.This study was supported by the following grant projects: GAUK 378421, 260 648/SVV/2023, and COOPERATIO Neurosciences.