Using serial-section electron microscopy and adaptive optics lattice light-sheet microscopy, Harvard Medical School (HMS) scientists have determined the function of the endolymphatic sac, a fluid-filled pocket connected to the rest of the inner ear by a long, thin duct.
"Scientists have known about the existence of the endolymphatic sac for maybe 300 years, but it wasn't understood exactly what it does," Sean Megason, HMS associate professor of systems biology, said. "It's even often missing in models or textbook cartoons of the inner ear. We didn't set out to study it, but we became interested once we saw its striking behavior."
In a study published earlier this month in eLife, the team reported that the endolymphatic sac acts as a pressure-relief valve and is formed by a thin barrier of cellular projections that opens and closes to regulate the release of fluid from inside the inner ear. Their findings reveal a unique biological mechanism for maintaining fluid pressure and composition and may inform the study and treatment of disorders involving defects in inner ear pressure such as Meniere's disease, a condition marked by vertigo, hearing loss, and ringing in the ears.
All the structures of the inner ear are interconnected and filled with specialized fluid, which moves in response to sound waves or head movement. These subtle fluid movements are detected by sensory cells and converted into neural signals for the brain to process. Both the pressure and chemical composition of inner ear fluid must be carefully maintained, and certain disorders such as Ménière's disease are thought to stem from abnormal pressure fluctuations.
The team also suspects that this mechanism may be present in other organs, such as the eye, brain and kidneys, which also contain pressurized fluid-filled cavities. Of particular interest is the role of genes related to lmx1bb, which, when mutated in mice, cause kidney and eye problems. Mutations to lmx1 genes in humans have been linked to glaucoma, a condition where fluid builds up in the front part of the eye. A better understanding of lamellar barriers and pressure- relief mechanisms could help inform the study and treatment of these diseases, the authors suggest.
"This study was definitely a case of seeing is believing," Megason said. "It was very important to have cutting-edge microscopy on many different fronts. Each of these different microscope techniques gave us a different piece of the puzzle and when put together, we get the whole picture."