I took a B.Sc. degree in Computing Science in 1977 nad have been working with them ever since. Most of my experience has been with mainframes, designing and building large computer systems for big companies. Since about 1985 I've also got involved in PC and minicomputer work, including client/server applications.
I'm now a project manager/system designer for 
Lloyds TSB , one of the largest bank and insurance groups in the UK.
Recently I've become interested in the Internet and the WWW (as you can see) and I built the LHON website as an exercise in HTML.
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This page was last updated on 29 September 2006
The text below is to indicate the content of the main purpose of this site - to provide information on Leber's Hereditary Optic Neuropathy. These pages provide a summary of the current information on Leber's Hereditary Optic Neuropathy (LHON) , also known as Leber's Optic Atrophy (LOA) , Leber's Optic Neuropathy (LON) or Leber's Disease. It is often referred to as just Leber's for short.
They contain a non-technical description of Leber's and current research into causes of Leber's. There are also links to Leber's-related sites and scientific papers, and useful information for visually impaired peopleliving in the United Kingdom.
Leber's Hereditary Optic Neuropathy is a rare condition which can cause loss of central vision. It usually affects men, most commonly in the late twenties or early thirties, but the symptoms can happen at any age, to men or women.
Leber's Hereditary Optic Neuropathy was first described by Theodore Leber in the 19th century, but we only really started to understand the inheritance anc cause of Leber's in the late 1980's.
Usually Leber's affects one eye first, so central vision is lost in that eye over a period of a few weeks. One or two months later, the second eye is affected in the same way. The time when someone is losing their eyesight is often called the 'acute' period. After a few more weeks, the eyesight stops getting worse.
Although that describes the most common pattern for Leber's, it can also affect someone very suddenly, or can affect them more gradually over a period of years.
Leber's is a genetic condition, that is, it is passed down through the family. Not everyone in a family affected by Leber's will lose their eyesight, and we do not yet know how to tell who will get symptoms.
We do know that Leber's is inherited through a gene which is only passed on through the egg cell from the mother. Men cannot pass on Leber's Hereditary Optic Neuropathy to their children.
Leber's Hereditary Optic Neuropathy is linked to a number of genes, all in the DNA of structures called Mitochondria. These provide energy to the cells of the body. We believe that the particdular gene changes linked to Leber's Hereditary Optic Neuropathy lower the amount of energy available to the cells of the optic nerve and retina. These cells are damaged and can even die because of theis lack of energy. The damage to the optic nerve and retina is what causes the symptoms of Leber's. Since about 1988 the research into Leber's Optic Neuropathy has been concentrating on understanding how it is passed on in certain families. There are many inherited (or genetic) conditions, but almost all of them involve genes in the nucleus of the cell. Many years ago a monk called Gregor Mendel studied how genes are passed on from parents to their offspring, and worked out a set of simple rules which can be used to predict how genetic conditions are passed on. These rules can normally be used to work out how likely it is for someone to develop a genetic condition, based on the family history and the pattern of who has (and has not) got the condition in a family.
Leber's Optic Neuropathy was a puzzle, because the pattern of inheritance in families does not follow the predictions of Mendel's rules. In the late 1980's it was realised that not all genes are held in the cell nucleus. Inside every cell of the body there are thousands of tiny objects called mitochondriaesponsible for releasing energy from food and making it available to the body. Mitochondria were found to contain their own genes, separate from the genes in the cell nucleus.
(The word mitochondriais pronounced mite-oh-kon-dree-ah and is used when we talk about more than one. If we are only talking about one, we use the slightly different word mitochondrion.)The genes in every cell nucleus come from both parents, but the mitochondria are only passed on by the mother. Scientists started analysing the mitochondria of people with LHON, and found that there are changes (called mutations) in the genes of their mitochondria.Once this was realised, scientists had an explanation for why LHON is only passed on through the mother and why it did not fit any of the patterns predicted by Mendel. His work only applied to genes which come from both parents. There is now a special kind of inheritance called mitochondrial inheritance, and several genetic conditions are now known to be inherited in this way. Since then, there have been many studies of people with LHON and their families, and we now know that there are at least 18 different changes in genes linked to LHON, but only 3 of these changes account for almost all the known cases. The other 15 gene changes are found in people who also have one of the 3 main changes. The 3 main changes are called the primary LHON mutations.
Genes are physically stored in the body using a special chemical called DNA. This is a complicated chemical, but can be thought of as an incredibly long, thin structure that, when magnified, looks a bit like a twisted ladder. Put simiply, each gene is a rung on the ladder. Scientists can count along the 'ladder' and identify each gene by the number of the 'rung'. The three main genes linked with LHON are called the 11778, 3460 and 14484 genes. This numbering system is not the only way of naming genes. Some people name genes by their purpose in the body, or the name of the chemical which the gene tells the body to produce. In this website I will tend to stick to the numbering system mentioned above, but in scientific papers the LHON genes are sometimes given other names. They are still talking about the same genes. The LHON genes are known to be the blueprint for part of a chemical called NADH Dehydrogenase or ND for short. This is a big chemical made up from smaller building blocks called sub-units. The sub-units are numbered, and we know that the 11778 gene is involved in making sub-unit ND4 so it is also known as the ND4 gene. The 3460 gene is also known as ND1 and the 14484 is also known as the ND6 gene. All genes are codes tellling the body how to make important chemicals called proteins. Every protein is made up of smaller chemicals called amino acids. Each protein is like a string of beads, where each bead is an amino acid. Each tiny part of a gene represents the amino acid to use for that 'bead'. In the case of the mitochondrial DNA, the 11778 gene normally tells the body to use the amino acid called arginine in a particular position in the chemical ND4.If the 11778 gene is the LHON mutation, then it does not represent arginine, but instead tells the body to use a different amino acid called histidine. The ND4 protein sub-unit created from this gene is very slightly different from the ND4 protein sub-unit made from the 'normal' gene. This difference makes the protein less good at doing its job. Each of the LHON mutations slightly change the structure of the protein created inside the mitochondrion.
The proteins inside the mitochondrion affected by LHON genes have a vital job. They are part of a very complicated mechanism that takes energy from food and makes something called ATP. This is the 'fuel' of the body. Whenever a cell in the body needs energy to do some work it uses up some ATP and relies on the mitochondria to make it some more. The process used to make ATP in the mitochondria is called oxidative phosphorylation.
When someone is affected by one or more LHON genes, the mitochondria in their body have altered proteins. These altered proteins are not so good at making ATP, so the cells in the body have less 'fuel'.
Some parts of the body need more energy, or more 'fuel', to do their normal job. These include muscles (especially the heart) and the nervous system (especially the eye nerve and retina). These are the parts of the body most often affected by mitochondrial genetic diseases like LHON. At first testing for these genes was difficult and only done in specialist laboratories around the world, but the techniques are becoming more common. Some recent studies have tried testing for the LHON genes in people with eye conditions not diagnosed as LHON, and found that the genetic tests can be valuable in identifying who actually has LHON and who does not. The tests are still complicated and time-consuming, and can take weeks or even months before the results are known. Sometimes a doctor can diagnose LHON from the family history of blindness in a sufferer's maternal relatives, but the genetic DNA tests are now thought to be the conclusive diagnostic proof that a LHON gene is present in a family.One of the major puzzles still being researched is that many people in a family may be carrying a LHON gene, but only a few of them actually develop symptoms of LHON. We do not yet know what extra factor triggers loss of eyesight. Most affected people are men, at least in families of European descent, and again no-one really knows why. There are some examples which suggest that certain things can trigger loss of eyesight. Examples quoted include: exposure to environmental poisons heavy smokingheavy drinkingpoisonous fumes metabolic illnesses like DiabetesPsychological or physiological stressAt the moment there is no way of predicting which people carrying a LHON gene will actually go on to lose their eyesight, or how badly their eyesight will be affected. There are some studies which have followed the medical history of family members for many years to try and build up statistics on the risk of developing symptoms, but the results of these studies are not very clear as yet. There are some other symptoms linked to the LHON genes which can be seen in family members of affected people. An example is changes in the blood vessels at the back of the eye. As these are seen in people who later lose eyesight and in people who never lose eyesight, they cannot be used to predict loss of eyesight. Some studies have found other symptoms in people carrying LHON genes, such as muscle tremors, tiredness and numbness of limbs. There has also been a suggested link with Multiple Sclerosis (MS). It is suggested that, although MS is NOT linked directly to the LHON genes, both LHON and MS are more common in people with certain European ancestry. That is, LHON is more common in people with maternal ancestors from Europe, and so is Multiple Sclerosis. It may be that one or more mitochondrial genes is linked to the cause of Multiple Sclerosis. There does not seem to be any direct link between LHON and MS. Unfortunately there is no proven treatment or cure for Leber's Hereditary Optic Neuropathy. A small percentage (about 4% for people with the 11778 gene) of people affected by Leber's recover some or all of their eyesight without any treatment at all. This recovery, if it happens, can be months or even a few years after the eyesight is lost. We do not know why some people recover and others do not. The chance of recovery without treatment does seem to be a little better for someone with the 3460 or 14484 gene rather than the 11778 gene, and for people who lose their eyesight while young. It is recommended that anyone who is at risk of eyesight failing due to Leber's avoids risks such as alcohol, tobacco or other environmental poisons. It may also help to keep stress levels low by relaxation and rest, especially if the eyesight does start to fail. A diet with a good balance of ingredients is always recommended for good general health, and keeping up the amount of fresh fruit and vegetables may be particularly important for someone at risk. Anti-oxidants such as Vitamin A, Vitamin C and Vitamin E may help to protect the vulnerable optic nerve from damage. Some people recommend 'alternative' food supplements such as additional anti-oxidants vitamins and Gingko Biloba. Injections of Hydroxycobalamin (Vitamin B12) while the eyesight is actually getting worse may help reduce the symptoms.
Injections of steroids used to be used to treat the swelling of the optic nerve during the period when eyesight is failing. This is no longer recommended. A chemical called Co-Enzyme Q10 has been tried as a treatment, but is again no longer recommended. One promising line of research is related to the way in which mitochondria, and so their DNA, are inherited. Every gene in the cell nucleus has two copies, one inherited from the father and one from the mother. Every cell in the body has the same genes in the nucleus. However, there are thousands of mitochondria in each cell, and each mitochondrion has many copies of each mitochondrial gene. That means that every cell in the body has thousands of copies of each mitochondrial gene. Unlike the genes in the nucleus, not every copy is the same. We all start off as a single cell - the fertilised egg. All of the mitochondria in this cell came from the mother, but not all of these mitochondria have the same genes. When this single cell divides to form two, then they divide to form four, and so on, each new cell has to have mitochondria. The mitochondria reproduce themselves so that each new cell gets itsquota of mitochondria. If someone is carrying one of the LHON genes, then some of their mitochondria have the copy of the gene which can lead to LHON , but some will have the 'normal' copy of the gene. As that person grows from a single cell to an entire adult body, there are millions of cells produced, and every time a new cell is produced, it will randomly get a mixture of 'LHON' and 'non-LHON' carrying mitochondria. That means that the adult body may end up being a mixture of cells with many LHON affected mitochondria, and cells with few, or even no LHON-affected mitochondria. This mixture of cells throughout the body is called heteroplasmy. The proportion of LHON-affected mitochondria which end up, by chance, in the optic nerve and retina of a person carrying a LHON gene, may be an imporant factor in deciding if they will eventually lose eyesight.
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