1. Determine the possible association between different types of optic nerve injury and mitochondrial DNA mutations and/or mitochondrial respiratory dysfunction [Our preliminary work showed an association of mtDNA mutations and NAION.  Please see attached article, which was recently published in Neurology].  Since we are the first investigators to report such an association, there is a possibility that this association is ethnically based (i.e. exists in only the Saudi population). This highlights the importance of identifying mutations that may be specific to our population. Our next step is to determine the possible link between mtDNA mutations and other optic nerve diseases, including glaucoma, optic neuritis, radiation optic neuropathy and toxic optic neuropathy.
2. Determine the spectrum of mitochondrial mutations in the Saudi population associated with various optic nerve diseases. Preliminary data for LHON indicates that the Saudi population possesses a different spectrum of mitochondrial mutations from other world populations and that at least two of the three common primary LHON mutation, present in 90% of LHON cases worldwide, are rare in the Saudi LHON patients. Identification of novel mutations in our population may help to confirm the clinical diagnosis for these disorders, particularly for LHON and NAION, and possibly for other disorders as well.
3. The results obtained from the Objectives 1 and 2 will help us to design a NanochipÒ (electronic microarray) specific for Saudi patients with various optic neuropathies.  NanochipsÒ are tiny silicon plates capable of rapid identification of 100 different DNA sequence variants in a patient’s DNA. The process is fast and accurate and the system was recently acquired by the Department of Genetics, Research Center, King Faisal Specialist Hospital. Once we identify mtDNA mutations common to our patient group, a NanochipÒ will be designed accordingly and offered for future use as a diagnostic services. Such a chip will greatly help in diagnosing mtDNA mutation in Saudi patients with various optic neuropathies. Note that this chip will be specific for the Saudi population.
4. It is now clear that mitochondrial DNA mutations are associated with at least LHON and NAION, but the reason for this association between mitochondria and optic nerve injury is still not clear.  Elucidating this link is the ultimate goal of our research.  When the link between mitochondrial DNA mutation, mitochondrial functional disturbance, and optic nerve injury is better understood, we will begin to assess possible treatment options.  This may be particularly important in glaucoma, where tens of thousands of Saudi’s are affected and current treatment is frequently inadequate to prevent profound visual loss

Thomas M. Bosley, MD,Jose Morales, MD

To be added.

King Faisal Specialist Hospital & Research Center

N/A.

"Increased relative mitochondrial DNA content in leucocytes of patients with NAION",  K K Abu-Amero, T M Bosleyin  British Journal of Ophthalmology bj90332 Module 4, "Mitochondrial DNA nucleotide changes innon-arteritic ischemic optic neuropathy" Thomas M. Bosley, MD; Khaled K. Abu-Amero, PhD; and Pinar T. Ozand, MD, PhD (NEUROLOGY 2004;63:1305–1308), "Mitochondrial T9957C Mutation in Association with NAION and Seizures but not MELAS",  Khaled K. Abu-Amero, Thomas M. Bosley, Saeed Bohlega, Erik Hansen (Ophthalmic Genetics, 26:31–36, 2005)

N/A.

N/A.