ARVO 2025 presentation: Combined administration of BDNF and CNTF provides superior neuroprotection as compared to BDNF alone in a mouse optic nerve crush model
Glaucoma, a leading cause of blindness and visual impairment worldwide, is characterized by progressive loss of retinal ganglion cells (RGCs) and damage to the optic nerve. Neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), have been extensively studied for their potential to promote RGC survival and axonal regeneration. However, BDNF's efficacy is restricted by receptor desensitization, while CNTF alone often induces inflammation and gliosis, limiting its therapeutic potential. This study was aimed at evaluating if a combination of BDNF and CNTF offers synergistic effects, providing superior neuroprotection as compared to either factor alone.
Methods
Optic nerve crush (ONC) was induced in C57BL/6JRj mice by crushing the right optic nerve with self-closing forceps for a duration of three seconds. BDNF alone or a combination of BDNF and CNTF were administrated as a single unilateral intravitreal (IVT) injection into the right eye immediately and three days after ONC. Spectral-domain optical coherence tomography (SD-OCT) and pattern electroretinography (PERG) were conducted at baseline and seven days after ONC induction. Seven days post-ONC eyes were enucleated, and retinal flat-mounts were stained with RNA-binding protein with multiple splicing (RBPMS) to quantify the number of RGCs.
Results
By day seven, significant changes were observed in saline-treated animals as compared to naives: thinning of the inner retina, decreased visual function, and RGC loss. Combined administration of BDNF and CNTF significantly alleviated thinning of the inner retina as compared to both saline-treated animals (p<0.01) and BDNF-only-treated animals (p<0.05). BDNF and CNTF co-treatment preserved pERG amplitude as compared to baseline measurements (p=0.19), whereas in BDNF and saline treated mice PERG amplitude was significantly decreased by Day 7 post-ONC as compared to respective baseline measurements (p<0.001 and p<0.05). RGC density was significantly higher in the BDNF and CNTF-combined treatment group as compared to saline-treated mice (p<0.01).
Conclusions
Our data suggest a superior efficacy of the combined BDNF and CNTF treatment in alleviating the thinning of inner retina, attenuating RGC loss, and preserving visual function in the mouse ONC model as compared to BDNF-only treatment.
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Authors
Inesa Lelyte, Symantas Ragauskas, Tomas Paulauskas, Marius Dragasius, Giedrius Kalesnykas
