Hereditary Hearing Loss: A Surprising Effect of a Diuretic in Mice
Could a medicine commonly used to remove excess fluid from the body help protect the delicate sensory cells responsible for hearing? A study published in 2025 revealed a surprising effect of furosemide, a well-known diuretic, in mice with a genetic form of hearing loss.
Researchers found that the medication reduced the loss of sensory hair cells in the inner ear of mice carrying a mutation in the TMPRSS3 gene.
The finding is intriguing, particularly because furosemide itself can sometimes cause hearing-related side effects.
But what exactly did the scientists discover, and could this research eventually lead to new treatments for hereditary hearing loss?
What is hereditary hearing loss?
Hereditary hearing loss occurs when changes in certain genes affect the development or function of the auditory system.
These genetic changes may influence different structures involved in hearing, including the sensory hair cells of the cochlea, the spiral-shaped organ within the inner ear.
Hair cells play a crucial role in converting sound vibrations into electrical signals that can be transmitted to the brain.
When these cells are damaged or lost, sensorineural hearing loss may develop.
Some forms of hereditary hearing loss are present from birth, while others become apparent during childhood or adulthood and may progress over time.
Researchers have identified numerous genes associated with hearing impairment. One of these is TMPRSS3.
What is the TMPRSS3 gene?
The TMPRSS3 gene provides instructions for producing a protein involved in the normal function of the inner ear.
Certain disease-causing variants of this gene are associated with autosomal recessive sensorineural hearing loss, meaning that the affected individual generally inherits a disease-causing variant from each parent.
TMPRSS3-related hearing loss can present in different ways:
DFNB10: typically associated with severe or profound hearing loss from birth or early life.
DFNB8: associated with hearing loss that develops later and may progressively worsen.
Although the genetic cause has been identified, scientists are still investigating precisely how TMPRSS3 dysfunction leads to the degeneration of cochlear hair cells.
Understanding this process is important because it may reveal opportunities to protect these cells before irreversible damage occurs.
Why is the electrical environment of the inner ear important?
The cochlea contains a specialised fluid called endolymph, which has a carefully regulated chemical composition and electrical charge.
An electrical difference known as the endocochlear potential helps create the conditions necessary for hair cells to detect sound.
This electrical potential is essential for normal hearing.
However, the 2025 researchers discovered something unexpected in mice carrying a particular TMPRSS3 mutation.
During early development, these animals experienced an unusually early rise in the endocochlear potential.
Shortly afterwards, their cochlear hair cells began to degenerate rapidly.
The researchers suspected that this premature change in the electrical environment could contribute to hair-cell death.
They therefore asked an important question:
Could reducing the endocochlear potential temporarily help protect these vulnerable cells?
What did the 2025 study discover?
The research was published in the Journal of Clinical Investigation by Shearer and colleagues.
The scientists investigated genetically modified mice carrying a mutation in the Tmprss3 gene.
In this mouse model, the sensory hair cells initially developed normally but underwent rapid degeneration around the time hearing normally begins.
The researchers explored several ways of modifying the electrical environment of the cochlea.
First, they examined inner-ear tissue under laboratory conditions and used additional genetically modified mouse models in which the normal endocochlear potential was reduced or absent.
These experiments showed that reducing the endocochlear potential could substantially improve hair-cell survival, even when TMPRSS3 function remained abnormal.
This provided evidence that the electrical environment of the cochlea contributes to hair-cell degeneration in this particular form of genetic hearing loss.
The scientists then investigated whether a medication could produce a similar protective effect.
Why did the researchers use furosemide?
Furosemide is a loop diuretic commonly used to treat conditions associated with fluid retention, such as heart failure and certain kidney or liver disorders.
It works primarily by increasing the amount of salt and water excreted by the kidneys.
However, furosemide also affects ion transport within the inner ear.
One of its known effects is a temporary reduction in the endocochlear potential.
The researchers therefore administered furosemide to young mice with the TMPRSS3 mutation during the period when their cochlear hair cells would normally begin to degenerate.
The results were encouraging:
Mice receiving furosemide showed improved survival of inner hair cells compared with untreated controls.
Some outer hair cells were also preserved, particularly towards the apex of the cochlea.
The results supported the hypothesis that modifying the electrical environment of the inner ear could reduce hair-cell degeneration.
However, the experiment involved a small number of animals, a short treatment period and a specific genetic mouse model.
The researchers demonstrated improved hair-cell survival, not restoration of normal hearing.
This distinction is essential when interpreting the findings.
Isn't furosemide potentially harmful to hearing?
Yes — and this is what makes the discovery particularly surprising.
Furosemide is known to have ototoxic potential, meaning that under certain circumstances it can adversely affect the auditory system.
Hearing impairment or tinnitus has been reported, particularly with high doses, rapid intravenous administration, impaired kidney function or simultaneous use of other ototoxic medications.
The drug can temporarily interfere with the electrical processes necessary for normal hearing.
So why might the same medicine protect hair cells in this experiment?
The answer may lie in the very specific conditions affecting the genetically modified mice.
In this model, the developing cochlea appeared vulnerable to a premature increase in its electrical potential.
Temporarily reducing that potential may have helped the sensory cells survive a critical developmental period.
This does not mean that furosemide generally protects hearing or that it is safe to use for hearing loss.
Its effects depend on the biological circumstances, and the doses used in animal experiments cannot be translated directly into treatment recommendations for people.
Does this mean hereditary hearing loss can now be treated with furosemide?
No. Furosemide is not an established or approved treatment for hereditary hearing loss.
The findings are important from a scientific perspective, but several questions remain unanswered.
Researchers still need to determine:
Whether the protective effect can be reproduced in further animal studies.
Whether preserved hair cells remain functional over the long term.
Whether treatment can improve measurable hearing outcomes.
Whether a safe and effective approach could eventually be developed for humans.
Whether the findings apply to other TMPRSS3 mutations or different forms of hereditary hearing loss.
There is also an important challenge: lowering the endocochlear potential may help protect vulnerable cells under certain experimental conditions, but a normal electrical potential is itself necessary for hearing.
A future treatment would therefore need to strike a delicate balance between protecting the sensory cells and preserving their function.
Why could this discovery matter in the future?
One particularly interesting possibility is that temporarily preserving cochlear hair cells could create a longer opportunity for other treatments.
For example, scientists are investigating gene therapies designed to address the underlying genetic causes of certain forms of hearing loss.
However, such approaches may be less effective if the sensory cells have already disappeared.
If researchers can identify safe ways to keep vulnerable hair cells alive for longer, this could potentially improve the opportunities for future genetic or molecular treatments.
This remains a research hypothesis rather than an available clinical strategy.
Nevertheless, the study highlights an important principle: understanding why sensory cells die may be just as important as developing methods to repair the responsible gene.
What does this research mean for patients today?
For people living with hereditary hearing loss, this study represents an interesting scientific development, not an immediate change in treatment.
Current management continues to depend on the type and severity of hearing impairment and may include:
Comprehensive audiological assessment.
Hearing aids when appropriate.
Cochlear implantation in selected individuals with severe or profound hearing loss.
Genetic assessment or counselling where clinically indicated.
Ongoing hearing monitoring and rehabilitation.
Patients should not take furosemide or change an existing prescription in an attempt to prevent hearing loss. Any use of this medicine should remain under appropriate medical supervision for its established indications.
The most important message from the study is that scientists are gradually gaining a better understanding of the mechanisms responsible for certain forms of genetic deafness.
A medicine known for its potential adverse effects on hearing has unexpectedly helped researchers uncover a possible way of protecting inner-ear sensory cells — at least in a specific mouse model.
Whether this discovery can eventually contribute to a safe and effective treatment for people remains to be seen.
Scientific references
Shearer AE et al. Endocochlear potential contributes to hair cell death in TMPRSS3 hearing loss. Journal of Clinical Investigation. 2025;135(18). DOI: 10.1172/JCI186395
U.S. National Library of Medicine, DailyMed. Furosemide Injection — Prescribing Information, Section 5.3: Ototoxicity. Drug safety information
