Mitochondrial DNA (mt DNA) supplies extranuclear (cytoplasmic) genes which program the manufacture of 13 of the 67 peptides of the mitochondrial respiratory enzymes. The remaining 54 are coded by nuclear DNA. All human children and adults, male and female, are entirely dependent on the cytoplasm of the ovum for their complement of mt DNA; the sperm contributes none. Accordingly, mutations in the mt DNA in a mother's ova will be passed on to all her children, although not all are clinically affected. Leber's hereditary optic neuropathy is in most cases due to a mutation that leads to the replacement of guanine by adenine at position 11778 in mt DNA. This causes histidine to be inserted instead of the normal arginine at the site of the 340th amino acid in the respiratory enzyme NADH subunit 4, hence its defective function. Other point mutations in the mt DNA coding for polypeptides of the respiratory chain complex or controlling sequences coded by mt DNA have been found in other families with Leber's hereditary optic neuropathy. Mitochondrial DNA is the site of other mutations as well. For ophthalmologists, the most important of these is the rare Kearns-Sayre syndrome (pigmentary retinopathy plus muscular dystrophies, especially of the extraocular muscles). Kearns-Sayre syndrome is due to deletions in the mt DNA, which vary in size and so affect a number of different respiratory enzymes, hence the variable manifestations. Cases are usually sporadic because the disease is often so severe that affected individuals do not reproduce if they survive, but in some cases inheritance from the mother has been reported.

Chromosome Aberrations↗

PubMedDate not supplied

Could do better: a curious clinician looks back--and forward.

A recently retired Scottish academic originally chose ophthalmology by a process of exclusion. Basic training in Glasgow and London was followed by "permanent" consultant appointments in Bristol, with a year as retina fellow at the Massachusetts Eye and Ear Infirmary, then London, then chairborne in Manchester and Edinburgh. Many opportunities for advances in ophthalmology were missed, but there were some successes: beta-blockers and steroid blockers in glaucoma, and gene mapping of one X-linked retinitis pigmentosa gene. Hypothesis-making is advocated by regarding no situation as static or sacrosanct, maintaining wide interests and collaborating with basic scientists.

History, 20th Century↗

PubMedDate not supplied

Close genetic linkage between X-linked retinitis pigmentosa and a restriction fragment length polymorphism identified by recombinant DNA probe L1.28.

Retinitis pigmentosa (RP) is a group of retinal degeneration characterized by progressive visual field loss, night blindness and pigmentary retinopathy. Its prevalence is in the region of 1-2 in 5,000 of the general population, making it one of the commoner causes of blindness in early and middle life. Although 36-48% of RP patients are isolated cases, the remainder show autosomal dominant, autosomal recessive or X-linked modes of inheritance. The X-linked variety ( XLRP ) is found in 14-22% of RP families in the UK. In the present study, X chromosome-specific recombinant DNA probes which can detect restriction fragment length polymorphisms have been used to localize the XLRP gene(s) to a subregion of the X chromosome using linkage analysis. One of the probes, L1.28, has been shown to be closely linked to XLRP in five kindreds, with 95% confidence limits of 0-15 centimorgans (maximum LOD score of 7.89 at a distance of 3 centimorgans). This suggests that the XLRP locus lies on the proximal part of the short arm of the X chromosome. This probe is potentially useful for carrier detection and early diagnosis in about 40% of cases, provided that genetic heterogeneity can be excluded by analysis of further families.

Chromosome Mapping↗

PubMedDate not supplied

Influence of dehydroepiandrosterone on rabbit intraocular pressure.

PURPOSE: The systemic concentration of dehydroepiandrosterone decreases with age in primates while in humans intraocular pressure (IOP) increases with aging. This study was designed to investigate if a relationship existed between dehydroepiandrosterone and IOP in pigmented rabbits. METHODS: Animals were treated unilaterally for 6 weeks with topical 3% dehydroepiandrosterone in 30% 2-hydroxypropyl-beta-cyclodextrin; the contralateral eye received vehicle alone. Drops were applied, and IOP measured, twice daily. RESULTS: Small, but statistically significant, drug-related effects were found. IOP was consistently higher in the afternoon; the afternoon minus morning difference in IOP, however, decreased with time. Topical, radioactive drug application indicated very low level penetration into aqueous humor, iris, corneal epithelium, the rest of the cornea, or bulbar conjunctiva. CONCLUSION: The small drug-related effects may be due, in large part, to poor intraocular drug penetration. The circadian rhythm of IOP appears to be time-dependent in chronic studies with a gradual loss of IOP difference between a.m. and p.m. readings.

Adjuvants, Immunologic↗