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Douglas Wallace's ground breaking work in the late 1980's on Mitochondrial DNA (mtDNA) mutations in Leber's Hereditary Optic Neuropathy helped clear the way for a fresh approach to understanding Optic Nerve Disease in general as well as other degenerative processes in nerve, brain, muscle, heart and other systems. Worldwide, work continues on mitochondrial [MitoMap.org] as well as chromosomal genetic factors in all the optic nerve diseases. The huge Human Genome Project hopes to unravel many fine details of disease processes. The Online Mendelian Inheritance in Man site documents progress in understanding all human genetic disease.
The frequency and pattern of occurence of disease in different population groups may give clues to disease triggers and risk factors. For example, according to population surveys, insulin resistance is a significant risk factor for open angle glaucoma. Glaucoma is more common and younger in onset in Americans of African heritage than their compatriots. Why? The fact that LHON expression is more likely in men than women mtDNA mutation carriers and expression rates vary in different populations is cause for much speculation and some, but not enough research. Some areas of the world, e.g. Cuba and Tanzania, seem to produce outbreaks of optic neuropathy. Nutritional, toxic, or unknown genetic factors are suspected.
Studying family lines with optic nerve disease is vital for researchers to help unravel the genetic and environmental factors contributing to disease. Many important insights have been found, such as patterns of inheritance, different types of expression (phenotypes) of disease depending on particular mutations, the deleterious effects smoking and alcohol have on eyes and interaction of other diseases such as diabetes, vascular and other nerve diseases with optic nerve diseases.
No subject could be more fundamental to understanding mechanisms of optic nerve disease. In this old discipline new important discoveries are still being made. The details of microanatomical retinal and optic nerve pathways may point to likely disease processes be they neuroreceptor up- or down-regulation, axonal transport defects, microcirculation changes or lamina cribrosa pressure points. (See the Webvision site for retinal neuroanatomy.)
The nervous system, of which the eye is a part, is a complex world of neurotransmitters, receptors, electrical energy gradients, transcription and translation regulators, membrane protein enzymes and channels, signal transducers, up regulators, down regulators, growth factors, chemical transport mechanisms, organelles, junctions, gaps, etc. Describing in detail the normal harmonious functioning of all the working parts of the nervous system is the huge job of the physiologist. The physiology of healthy nerves contains clues regarding toxic, nutritive, hormonal, ageing and drug effects in disease. Why are retinal ganglion cells (RGCs) prone to death in optic nerve disease? More specifically, why are P type midget system RGCs selected for destruction in LHON and M type RGCs more susceptible in Glaucoma? Perhaps the neurophysiologists can tell us.
These disciplines identify and describe the components of living cells, their functions in the cell and their differences among different cell types. They lie at the core of our understanding of conception, growth, disease, degeneration and death of all living things. Intensive basic neuroscience research is centred around mechanisms of nerve cell life, growth and death in health and disease. One burning unanswered issue in LHON expression is the one of male predominance. There is a lack of genetic evidence for an X-linked genetic factor. Could the epigenetic factor be female hormonal effects on inhibitory neuro receptors?
Looking at diseased eye tissues under microscopes using special stains, markers and equipment and analyzing eye tissue samples borrows from advances in neuroanatomy, histology, neurophysiology and cell biology to learn exactly where and how optic nerve disease occurs. e.g. Glutamate neurotransmitter excitotoxicity seems to play a role in Glaucoma and ischaemic optic neuropathy as shown by higher glutamate levels found in the vitreous humour of glaucomatous eyes. Is this also the case for LHON and toxic optic neuropathy? Is the massing of mitochondria found in electron microscopic sections of LHON optic nerves compensating for their inefficient energy production? Non invasive techniques of studying live human eyes' diseased tissues are advancing our knowledge of optic neuropathies.
It is critical to a patient's outcome that any optic nerve disease be diagnosed early and accurately. Research is refining methods to quickly differentiate syndromes with similar presentation so that early appropriate treatment may be offered.
Work on refining techniques to scan the detailed structure and function of living eyes and optic nerves may give us more warning in monitoring disease processes and give us the knowledge to better understand and treat optic neuropathies.
We have witnessed the revolutionary success in the preventive medicine approaches to the big killers, blood vessel disease and cancer. These include eating the "correct" variety of food [e.g. Mediterranean diet] including vegetables and whole fruits, nuts, fibre, whole fat dairy, adequate protein and beneficial fats [e.g. olive oil, fish oil and medium chain triglycerides], vitamin supplements, anti oxidants and avoiding carbohydrate excess, and ingested and inhaled toxins. Insulin resistance syndrome appears to be a major fundamental risk factor for most of these common diseases. Much epidemiology and biochemistry lies behind this knowledge. Much of this applies to optic nerve function too. The time is past due for research into preventive and rescue dietary therapy for glaucoma and LHON.
In glaucoma intra ocular pressure reducing drugs delay retinal ganglion cell (RGC) loss but disease tends to progress anyway. New concepts in RGC preservation in glaucoma as well as brain cell preservation in stroke and trauma are being explored which may have implications for the other optic neuropathies. Insight gained from studying the mechanisms underlying toxic optic neuropathies could be applied to treating other optic neuropathies and retinopathies. For example:
Infections can play a role in precipitating optic nerve disease. For example, transverse myelitis, one cause of Optic Neuritis can be brought on by infections such as Mononucleosis (Epstein-Barr Virus, Cytomegalovirus). Recently it has been found that people with Human Immunodeficiency Virus (HIV) can have visual field losses consistent with Optic Nerve Disease before any other evidence of Aquired Immune Deficiency Syndrome (AIDS) is seen. The injury mechanism is not determined. In full blown AIDS neurologic abnormalities including Optic Nerve disease consistent with the progressive diffuse leukoencephalopathy (PDL) in the brains of AIDS victims are being studied. Tumour necrosis factor is postulated to play an important role here. Animal models are used to study this. Prion disease has barely been considered a factor in human eye disease, but it is known that inoculation of scrapie into conjunctiva can cause neural inflammation in rodents. Neurocysticercosis (brain tapeworm disease), the most common parasitic infection of the brain, can cause optic neuropathy.
Time honoured anterior chamber pressure relief surgery, trabeculectomy, in high tension glaucoma can be sight saving. More recent study shows that pressure relief around the optic nerve itself, optic nerve sheath fenestration, is not indicated in acute ischemic neuropathy. Experimental research going on now gives hope for future nerve transplants, implants, nerve regeneration, gene transfer/repair, artificial eyes, and brain cortex stimulators as solutions to optic neuropathy vision loss.
Braille is not yet superceded, but they're working tools to circumvent blindness.
If blind people can see in their dreams, shouldn't it be possible to make reality a dream and thereby turn their dreams of sight into reality? In humans seeing is a large part of consciousness. People from such diverse fields as cognitive psychology, neuroanatomy, functional brain imaging, single cell neurophysiology, computer science, biomechanical engineering, artificial intelligence, mathematics, philosophy and quantum physics are asking the questions: what is consciousness and how does it work? When we close in on the answers to these questions we will be closer to our dreams.
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