Over ninety percent of all LHON cases carry one of the three main LHON Gene Mutations. The rest carry one of the many rarer mutations, or a mutation which has not been found yet.
But just carrying one of the LHON gene mutations is not enough to be affected by LHON. Most carriers are never affected, especially female LHON Carriers.
Sometimes the “trigger” for the onset of LHON seems clear, like treatment with Ethambutol, Erythromycin or some other powerful drug.
Most of the time we simply do not know why someone can have normal eyesight for years, then suddely develop LHON.
This proposal is that there are some factors we know about and some we do not know about.
Some factors add to the risk of LHON, others protect us from LHON.
If the factors causing LHON outweight the factors protecting a person from LHON, he or she will be affected.
This presentation tries to illustrate this idea.
There are still many unanswered questions.
Some scientists believe that someone who has inherited a LHON gene must have a minimum percentage of affected mitochondria to develop LHON. This percentage seems to be arount at least 80 percent and may be as high as 95 percent Affected mitochondria. (2575667)
Once LHON is “triggered”, the outcome does not depend on the percentage of affected mitochondria.
The Puzzles of LHON Triggers
Researchers have learned a lot about LHON in the last few years, but there are still puzzles to be answered.
Why are so few LHON Carriers affected?
Researchhers estimate that about 1 in every 8,500 people carries a LHON causing mutation, but only about 1 in 30,000 to 50,000 develop LHON.
One theory is that the cells of LHON Carriers have more mitochondria to compensate for the less efficient mitochondrial protein. This creation of extra mitochondria is called mitochondrial biogenesis. (24369379)(24501072)
Why are the Retinas and Optic Nerves affected?
There is a theory that LHON mutation is present in all tissues, but the only tissues affected are the ones with the highest energy demand. However, the same theory has been put forward to explain why Parkinson’s Disease affects cells in the brain controlling motion.
Do the LHON mutations make the cells more susceptible to light damage? The tissues affected are the ones that light travels through to reach the rods and cones in the retina.
Why are women carriers affected much less often than men?
Extrogen seems to protect against the effcts of a LHON gene, but not completely.
Why does LHON affect the eyesight at a particular age?
The majority of people affected by LHON first lose eyesight in early adulthood.
Why is the eysight not affected from birth? The energy demands of the retinas and optic nerves are there from birth.
Is this due to an age-related metabolic change, such as the end of the male adolescent growth spurt? Is it due to a change in fat metabolism, A change in Calcium metabolism?
We know the general pattern of age from many scientific papers, but is there any consistency in the age affected for a particular family?
If the age affected is driven by a gradual factor such as a build up of affected mitochondria, or a build up of damage due to Reactive Oxygen Species, why is it so consistent? Why are the eyes not both affected at the same time?
Why is one eye affected significantly after the other?
Whatever the trigger, why is there a delay between the eyes being affected? Why are they not both affected at the same time?
Is this related to the dominant eye? If for some reason LHON only affects the dominant eye, and the brain switches to the other eye being dominant because of the LHON damage, this could help explain the difference.
What is different in families with early-onset LHON?
Is there a second genetic factor making these people especially likely to be affected?
Is some protective factor missing?
Why are some people high risk but never lose eyesight?
How can some people have a LHON causing mutation, smoke, drink heavily for years but never be affected?
Do they have an extra protective factor?
Do they lack an extra LHON-causing factor?
Why is LHON present in 100% of cell cultures / animal models but not in all human carriers?
There are cell cultures and mouse models used to study LHON. The lab tests show that these cultures are affected by the LHON gene.
What is it about these cultures or mouse strains that makes them 100% susceptible to LHON?
The assumption is that the LHON gene is affecting the cell and animal models in the same way it affects humans, but is this true?
This page was last updated August 31 2015