All the better to hear you with, my dear

The hearing loss associated with Norrie Disease (ND) is a particularly nasty symptom of this genetic disorder.

A blind person relies heavily on his/her sense of hearing for performing everyday tasks. Additionally, music is a favorite pastime for most blind people. To make matters worse, the hearing loss in ND does not present a stable situation, being progressive in nature.

Past research (Rehm et al., 2002) has established that in ND the damage to the ear happens in a part of the inner ear called the stria vascularis.

Now, I have heard of the cochlea, but what on earth is the stria vascularis?

A bit of of reading reveals that the stria vascularis is a highly vascular tissue within the cochlea.

Ok, that makes sense to me. The problem of ND is essentially a problem with the development and/or maintenance of the fine network of blood vessels which distribute blood within tissues (microvasculature). So ND would cause a loss of blood vessels in the stria vascularis, which would prevent the stria from doing whatever it is supposed to do, which would somehow result in a loss of hearing.

This is all a bit vague. I like digging deep into problems, so I read a bit more. I present a more in-depth explanation of the functioning of the stria vascularis in the boxed section below, which you may skip if you wish.

The inner ear consists of a complex series of tubes, running through the temporal bone of the skull. The bony tubes (sometimes called the bony labyrinth) are filled with a fluid called perilymph (shown in orange in the diagram below). Within this bony labyrinth is a second series of tubes, filled with a fluid called endolymph (shown in blue). So, this is a tube within a tube – each tube containing a different fluid. [Source: Histology website of the Southern Illinois University School of Medicine]   The cochlea is part of the inner ear. It is a spiral structure (clearly visible in the above diagram) which resembles a snail (In fact, the word cochlea is derived from the Greek word kokhlias for a snail). Found on the lateral wall of the cochlea, the stria vascularis is a highly vascular tissue which produces the endolymph. It is one of the most highly vascularized tissues found in the adult mammalian body (Zdebik et al., 2009). So what’s the significance of this? Well, the two fluids – perilymph and endolymph – have different ionic concentrations. Endolymph is rich in potassium, whereas perilymph is rich in sodium. This gives rise to a positive voltage (called the endocochlear potential or EP) of 80 - 100 mV seen in the endolymphatic space of the cochlea. If the stria was unable to produce endolymph, that would result in a loss of EP. Here is a nice little analogy to explain EP: If you hold a brick up in the air, it has available (potential) energy: if you drop it, that potential will be turned into actual energy when the brick hits the floor and makes a sound and a dent. Electrochemical potential is also a kind of available energy, waiting for an opportunity to do work. In the cochlea, electrochemical potential arises because there are different charges within fluid compartments of the inner ear, creating a flow of electric current as they try to equalize. The cochlea – or to be more precise, the specialized sensory cells (hair cells) within the cochlea – is/are responsible for converting sounds which enter the ear canal, from mechanical vibrations into electrical signals (this process is called transduction), which are then carried to the brain by the auditory nerve. It is endocochlear potential which is the driving force or ‘battery’ for the cochlear hair cells.   In other words, stria vascularis acts as a remote “power plant” to generate the energy necessary for sound transduction (Zdebik et al., 2009). So loss of function of Norrin results in loss of blood vessels in the stria vascularis, which means the stria vascularis cannot do its job of producing endolymph properly, which results in loss of endocochlear potential, which leads to loss of transduction, which signifies loss of hearing. Got it!

So if scientists could inject a good copy of the gene Ndp in the inner ear, could that stop the hearing from deteriorating? Better still, could that reverse the hearing loss which has already taken place?

Probably. Maybe.

Until fairly recently, no one knew how to deliver a gene to the inner ear. Since there are more than 300 genetic defects which are known to prevent the hair cells in the human inner ear from working properly, a lot of research is going on, on how to restore hearing when it is lost due to a genetic defect. The latest news is, that scientists have managed to restore hearing in a mouse model of Usher syndrome. They have managed to do this “by using a modified, non-pathogenic adeno-associated virus (Anc80L65), which is introduced into the ear by way of a "Trojan Horse" to deliver genes to restore the functionality of the damaged hair cells” [Source: ScienceDaily

But there is still a long way to go. Translating this research from mouse to humans is going to take some time. The inner ear in humans is located within a cavity in the temporal bone of the skull. The temporal bone is one of the densest bones in the human body. How to deliver the virus to the human cochlea is one of the questions which remains to be answered.

And then the research needs to be applied to the specific case of Norrie disease. To the best of my knowledge, thus far there is no research specifically targeting the hearing loss associated with ND.

However, I do know that the Norrie Disease Association is trying very hard to get some research started on this symptom of Norrie disease, so I am keeping my fingers crossed.

Fingers crossed, toes crossed, everything crossed.

Till next time then,

Meenu.