^ L-Type Calcium channel
Wikipedia Calcium channel
Wikipedia Voltage dependent calcium channel
^ Lamina Cribrosa sclerae Layer of connective tissue continuous with the sclera through which the retinal ganglion cell axons pass in the anterior part of the optic nerve. This area roughly coincides with the point where the retinal ganglion cell axons aquire their myelin sheaths and with abrupt changes in mitochondrial numbers. As a result of this unique anatomy, theories of retinal ganglion cell death often revolve around this disc. Stem cells are found here
A. Bristow, P.G Griffiths, R.M. Andrews, M.A. Johnson, D. Turnbull. The relationship of mitochondrial activity to structure and function of the optic nerve. Arch Ophthalmol. 2003 Sep;121(9):1342-3. PMID 12049585
Bernstein, SL; Guo, Y; Kerr, C; Fawcett, RJ; Stern, JH; Temple, S; Mehrabian, Z. “The optic nerve lamina region is a neural progenitor cell niche.” Jul 28, 2020. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.2001858117
^ Lateral Geniculate Nucleus Major terminus of retinal ganglion cell axons. A nucleus of synapses in the thalamus. Divides into 6 layers with intercalated zones. There are four superficial parvocellular layers and two deeper magnocellular layers. The midget cell axons from the macula terminate in the parvocellullar area. The more peripheral parasol cell axons terminate in the magnocellular zones.
^ Laurence-Moon syndrome A syndrome of mental retardation, pigmentary retinopathy, hypogenitalism, and spastic paraplegia.
^ Leber's Congenital Amaurosis (LCA) A group of autosomal recessive retinal pigment diseases manifest at birth. Also, "Retinal aplasia" and "Congenital retinal blindness (CRB)". Some classify it as the earliest form of Retinitis Pigmentosa. Apart from poor vision from birth, associated symptoms include nystagmus (uncontrolled roving eye movements), cataract and keratoconus. They are a common cause of retinal blindness in children. At least three gene heterogenecities localize to chromosome 17p13.1: guanylate cyclase gene, RPE65 and CRX. Pigment Epithelium Derived Factor (PEDF) is also possibly implicated. Loci on chromosomes 19, 14 and 6 are also implicated.
Gregory M. Acland, et al. Gene therapy restores vision in a canine model of childhood blindness. Nature Genetics, May 2001;28(1):92-5. PMID 11326284
Leber's Hereditary Optic Neuropathy
(LHON) (synonym Leber's Optic Atrophy) Optic nerve disease of
DNA (mtDNA) inheritance (i.e. maternal inheritance)
with peak incidence in males age 20's. Females are less likely to be
Central vision defects are predominant with centrocecal scotomata developing suddenly over a period of weeks or months. Presymptomatic colour vision loss has been described. Peripapillary microangiopathy is seen in acute stages on fundoscopy. With some mutations (esp. 14484 and 3460) a fluctuating course with spontaneous remissions is possible.
Penetrance is highly variable within populations and within families with heteroplasmy/ homoplasmy not explaining all variability. This provokes a search for secondary genetic and environmental factors.
Primary mutations are single mtDNA nucleotide replacements effecting the complexes of the respiratory electron transport chain. The generally agreed primary nucleotide mutations are:
Other mutations such as at 15257 of Complex III, at 9101 of Complex V, at 14482 of Complex I (Howell, et. al. Am. J. Hum. Genet., 62:196-202, 1998) and others are reported as primary pathogenic mutants.
Other point mutations are thought to be secondary, contributing to penetrance in the presence of the primary mutations.
Tobacco and alcohol ingestion are are highly suspect as environmental precipitators. Nutritional status, toxic poisons and drugs, trauma and incidental disease processes may also play a role in provoking optic neuropathy in carriers. The reason for the sex difference in disease expression is being researched. X-linked loci are thought to play a role. Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background and X-linked loci.
Diagnosis is based on history, physical findings, exclusion of other causes of optic neuropathy and genetic testing (Polymerase Chain Reaction).
No treatment has proven success.
IFOND LHON article
Hudson G, Carelli V, et al. Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background. Am J Hum Genet. 2007 Aug;81(2):228-33.PMID 17668373 PubMed central free full text
Hudson G, Keers S, Yu Wai Man P, Griffiths P, Huoponen K, Savontaus ML, Nikoskelainen E, Zeviani M, Carrara F, Horvath R, Karcagi V, Spruijt L, de Coo IF, Smeets HJ, Chinnery PF. Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder. Am J Hum Genet. 2005 Dec;77(6):1086-91. Epub 2005 Oct 11. PMID 16380918
Patrick Yu-Wai-Man, and Patrick F Chinnery GeneReviews Leber Hereditary Optic Neuropathy June 23 , 2016
John B. Kerrison and Nancy J. Newman. Clinical Spectrum of Leber's Hereditary Optic Neuropathy. Clinical Neuroscience. 4:295-301(1997) IFOND Reprint
^ Leber's Miliary Aneurysms Regarded as a later milder form of Coats disease or retinal telangiectasis. It usually affects only a small part of the central section of the retina. It does not affect side vision or color vision or night vision to any great extent. Patients do not go completely blind from this disorder. It is not related to Leber Hereditary Optic Neuropathy. Laser is often helpful.
Wikipedia Coats disease.
Leber's miliary aneurysms Oman J Ophthalmol. 2013 May-Aug; 6(2): 119–121. Walaa Alturkistany and Saad Waheeb
^ Leigh syndrome Leigh syndrome may include neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) other symptoms such as mental retardation may occur. There is focal brain stem necrosis and capillary proliferation. Various mitochondrial or chromosomal mutations may induce the syndrome. It has been associated with point mutations at mtDNA position 8993 affecting ATP synthase (complex V) subunit 6. This probably interferes with the hydrogen channel of ATP synthase. Also, several types of chromosomal genetic metabolic mutations have been described which can cause the Leigh syndrome. These include autosomal recessive and X-linked inheritance and involvement of enzyme complexes pyruvate dehydrogenase, complex I and complex IV (the most common).
^ Library, DNA A collection of small strands or templates of DNA used for amplification techniques such as the polymerase chain reaction to look for specific DNA sequences in a sample.
^ Ligand A small biomolecule which associates with a protein.
Linkage In genetics the association of genes on the same chromosome or nearby on the same
bit of DNA.
~disequilibrium When alleles (variants or mutants of a gene) at two or more nearby loci (places on a chromosome or DNA strand) may be found together more often than predicted from their frequency in the general population. That is, the gene variant types tend to stick together.
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