Belzutifan for treatment of giant retinal hemangioblastoma with extrascleral extension associated with von Hippel-Lindau syndrome.

PURPOSE: To describe the clinical response and safety profile of the novel HIF-2ɑ inhibitor belzutifan in treating a giant retinal hemangioblastoma (RHB) with extrascleral extension associated with von Hippel-Lindau syndrome (VHL). METHODS: A 71-year-old woman with VHL presented with a giant RHB with extrascleral extension in her only remaining eye. She had no light perception OD and intraocular pressure (IOP) was 48. She requested enucleation due to chronic pain, but, due to concern for significant bleeding given the size of the neoplasm, a trial of belzutifan was initiated. RESULTS: Within three months of treatment initiation, the patient reported an 80% reduction in pain. MRI showed 30% reduction in longest tumor diameter. Dose adjustments were guided by serum hemoglobin levels, allowing the patient to remain on the medication for over a year with continued tumor regression on MRI and avoid enucleation. CONCLUSION: RHB with extrascleral extension is exceedingly rare and its treatment is complex, often requiring enucleation or external beam radiotherapy. This report demonstrates the use of belzutifan to safely and successfully reduce ocular tumor burden of complicated RHB with extrascleral extension, ultimately decreasing the need for enucleation.

GABAergic neuronal IL-4R mediates T cell effect on memory.

Mechanisms governing how immune cells and their derived molecules impact homeostatic brain function are still poorly understood. Here, we elucidate neuronal mechanisms underlying T cell effects on synaptic function and episodic memory. Depletion of CD4 T cells led to memory deficits and impaired long-term potentiation. Severe combined immune-deficient mice exhibited amnesia, which was reversible by repopulation with T cells from wild-type but not from IL-4-knockout mice. Behaviors impacted by T cells were mediated via IL-4 receptors expressed on neurons. Exploration of snRNA-seq of neurons participating in memory processing provided insights into synaptic organization and plasticity-associated pathways regulated by immune cells. IL-4Rα knockout in inhibitory (but not in excitatory) neurons was sufficient to impair contextual fear memory, and snRNA-seq from these mice pointed to IL-4-driven regulation of synaptic function in promoting memory. These findings provide new insights into complex neuroimmune interactions at the transcriptional and functional levels in neurons under physiological conditions.