IMMUNOLOGY2025™ Conference Recordings-Targeted lymphatic stimulation without angiogenic toxicities

Targeted lymphatic stimulation without angiogenic toxicities - Eric Hoyeon Song

Video Transcription

Video Summary

The speaker, an ophthalmologist and immunologist, discussed research on how the central nervous system and eye are not truly “immune privileged,” but instead use lymphatic drainage for immune surveillance. In earlier work, the lab showed that stimulating CNS lymphatics with VEGF-C improved antigen drainage to cervical lymph nodes, boosted T-cell priming and trafficking, and enhanced anti-tumor immunity in brain tumor models, especially when combined with PD-1 blockade.<br /><br />The talk then shifted to the eye, where the speaker investigated how injected drugs drain from the vitreous and anterior chamber. They found that vitreous drainage reaches deep cervical lymph nodes and identified lymphatic vessels around the optic nerve sheath as a likely route. This supported a shared lymphatic connection between the eye and brain.<br /><br />A major focus was engineering a lymphatic-specific VEGF-C variant, LS-VEGF-C, because wild-type VEGF-C also activates VEGFR2 and causes unwanted blood vessel effects. Using directed evolution and yeast display, the team created a potent VEGFR3-selective agonist that promotes lymphatic growth without angiogenesis or vascular leakage. LS-VEGF-C showed benefits in models of glaucoma, lymphedema, and retinal injury, reduced reactive oxygen species, and even protected retinal ganglion cells after NMDA injury.

Keywords

central nervous system lymphatics

immune surveillance

VEGF-C

PD-1 blockade

optic nerve sheath lymphatics

LS-VEGF-C

retinal ganglion cells