Retinal degeneration driven by brain-derived neurotrophic factor deficiency in microglia and T-lymphocytes

TL;DR

This study shows that a lack of brain-derived neurotrophic factor in immune cells leads to retinal degeneration, suggesting new treatment approaches for diseases like glaucoma.

Contribution

The study reveals a novel role of BDNF from immune cells in retinal health and neurodegeneration.

Findings

BDNF deficiency in immune cells causes retinal ganglion cell and photoreceptor degeneration.

Aged BDNF-deficient mice show increased astrogliosis and synaptic changes.

Immune cell-derived BDNF is critical for retinal homeostasis.

Abstract

Neurodegenerative diseases, such as glaucoma or multiple sclerosis, are characterized by progressive neuronal loss involving diverse pathogenic mechanisms. The brain-derived neurotrophic factor (BDNF) has been implicated in neuroprotection and neural plasticity, yet its regulation and involvement in retinal neurodegenerative diseases remain largely unclear. In this study, we investigated the impact of BDNF deficiency in immune cells on retinal integrity. Using mice with a conditional BDNF knockout in microglia/macrophages and T-cells or selectively in microglia/macrophages, we analyzed retinal changes at 3 and 7 months of age, with wildtype mice as controls. BDNF-deficient mice exhibited early and progressive degeneration of retinal ganglion cells and photoreceptors, accompanied by pronounced astrogliosis, which was exacerbated in aged animals. In 7-month-old mice, adaptive changes in synapses could be documented, evidenced through enhanced expression of the vesicular acetylcholine transporter. These findings demonstrate that BDNF from immune cells plays a crucial role in maintaining retinal homeostasis and that its loss promotes retinal neurodegeneration. Targeting immune cell-derived BDNF may offer novel therapeutic strategies for retinal involvement in neurodegenerative diseases with implications for treatment of glaucoma or multiple sclerosis.

The online version contains supplementary material available at 10.1038/s41598-025-21423-6.

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