.. A Guide to the Genetics of ..
.. Leber's Hereditary Optic Neuropathy 'LHON' ..
.. a Mitochondrial Disorder of the Enzyme 'Complex I' ..
THE-LHON-ENIGMA A Computer Model of LHON
Below is a simple computer model that attempts to explain the enigmatic features of LHON.
Make your selections - and see what happens ! (Further details follow the model)
1. Click ON - to produce the display.
In this model the cells of the Optic Nerves are represented by 256 squares - with a clear square indicating a LIVE cell.
2. The default settings are 'Normal mtDNA', 'No toxicity/abuse/Malnutrition' and an 'Average Family History',
and these Selected Options are repeated on the display.
3. Next click on the 1>, 10>, 100>, >> buttons to increase the age - until 83 years and 3 months is reached.
With each click, the display will be updated
And, with the default settings it is extremely unlikely that any cells will die.
4. Perhaps now click on 'COMMON LHON' & 'NEW RUN' and see what happens as the age is increased.
And, this time it is likely that some cells will die.
Perhaps try several RUNs with these settings to see various outcomes.
5. Now try the model with various other of the Selected Options.
The model shows:
A person with Normal mtDNA does not have a significant Visual Deficit unless they also have a 'Severe Toxicity/Abuse/Malnutrition'.
But a person with a COMMON LHON mutation may get a significant Visual Deficit even with a 'Mild Toxicity/Abuse/Malnutrition'.
The results for persons with milder or more severe LHON mutations can also be found.
Changing the 'Family History' alters the sensitivity of the model - with a 'Good Family History' reducing any Visual Deficit.
The model can also show the effect of reducing exposure to toxic substances, avoidance of alcohol and smoking, and improving nutrition,
once a Visual Deficit has started to appear.
The model follows the premiss that a 'COMMON LHON' mutation reduces the efficiency of the enzyme 'Complex 1' by 50%;
and this brings the cells of the optic nerves close to the point at which they will die.
SEVERE exposure to toxic substances, abuse of alcohol and smoking, and malnutrition will also do this in normal persons.
However, a person with a 'COMMON LHON' mutation needs only MILD exposure to toxins, abuse of alcohol and smoking, or malnutrition
to suffer irreversible damage to the eyes.