Two medical eye researchers began a joint study around two decades ago that looked at eye muscle stimulation by their nerves.Along with Harvard Medical School work colleagues both researchers from the University of Iowa had been investigating subjects that suffered from eye movement disorders and as a result developed a mutated mouse subject to simulate the condition using the identified mutated genes. While the mutation was the same in the mouse subject as that displayed in the human patient, there was no underlying cause for it.
A study was then developed out of the original to develop the gene mutation to try an d pinpoint the time at which normal eye muscle development innervations departed from that of the mutants.
What they recorded was that it chronologically happened at a very early stage in development. In just the mutant mice a unique swelling in just one of the nerves to the eye muscle was found.
Further investigations of the swellings in the mice showed that they developed as fibers that extended to the eyes from the brain were attempting to leave the nerve as if they were already present in the eye socket.
The researchers reasoned that something must be transported more effectively by this mutation to the motor neurons trying to reach the orbit and the eye muscles, that something was causing the motor neurons to "assume " that they had already reached their target, that being the orbit of the eye.
A further mouse test subject was then developed that specifically lacked the protein and found no muscle innervation faults. After additional test mice were bred that were to carry the malformed proteins they discovered that the mice developed a normal innervation.
So with evidence to show what was going wrong and why, they still were unclear as to the possible product that was more effectively transported in the mutant mice and, by logical extension, in humans. Ongoing analysis showed that breeding the mutant mice with another mutant having eye muscle innervation defects could enhance the effect of either mutation.
With the mutated protein identified, and its enhanced function, they also had an idea of the likely cargo transported by the protein to allow normal innervation of eye muscles. This data provides the necessary level of understanding to design rational approaches to block the defect from developing.