The 100 most frequently cited articles in ophthalmology journals.

We screened 46 ophthalmology journals to identify the most frequently cited articles using the Science Citation Index Expanded (1975 to 2006). The 100 most-cited articles were published in 13 journals, most in the Archives of Ophthalmology (n = 30), followed by Ophthalmology (n = 27) and the American Journal of Ophthalmology (n = 11), and originated from 10 countries, led by the United States (n = 86). The topics covered by these classic articles included epidemiology of age-related macular degeneration and glaucoma, description of new diseases including cytomegalovirus retinitis, optical coherence tomography, hypotensive medications in glaucoma, laser photocoagulation to treat diabetic retinopathy and subfoveal choroidal neovascularization, photorefractive surgery, and vitrectomy to treat idiopathic macular hole. The most frequently cited articles provide a historical perspective in the scientific advancement of ophthalmology during the last 3 decades.

Nitric oxide synthase and superoxide dismutase gene polymorphisms in Behçet disease.

OBJECTIVE: To investigate the association of endothelial nitric oxide synthase (NOS), inducible NOS, manganese superoxide dismutase (SOD), and extracellular SOD gene polymorphisms with susceptibility to Behçet disease (BD) in Japan. METHODS: Seventy-eight consecutive Japanese patients with BD and 107 healthy control subjects were genotyped by polymerase chain reaction or polymerase chain reaction-restriction fragment length polymorphism methods for endothelial NOS polymorphisms in intron 4, exon 7, and promoter region; inducible NOS polymorphisms in exon 16 and promoter region; manganese SOD Ala16Val polymorphism; and extracellular SOD Arg213Gly polymorphism. HLA-B*51 alleles, which have been found to be associated with BD, were also determined. RESULTS: The frequencies of manganese SOD Val16 increased significantly in patients with BD. The manganese SOD-Val/Val genotype and HLA-B*5101 had a synergistic role in controlling susceptibility to BD. There was no significant difference in the frequencies of endothelial NOS, inducible NOS, and extracellular SOD gene polymorphisms between patients with BD and control subjects. CONCLUSION: The manganese SOD Val16 allele is associated with the development of BD in Japan. Extracellular SOD, endothelial NOS, and inducible NOS gene polymorphisms do not constitute a risk factor for developing BD in Japan. CLINICAL RELEVANCE: The manganese SOD gene polymorphism seems to contribute to BD.

Identification of a novel splice site mutation of the CSPG2 gene in a Japanese family with Wagner syndrome.

PURPOSE: To investigate the genetic basis and clinical variability of Wagner syndrome, a rare, dominantly inherited vitreoretinopathy. METHODS: Clinical examination, linkage analysis, and mutational screening were performed in a large, three-generation, consanguineous Japanese family with Wagner syndrome. The effect of splice site mutation was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis with lymphoblastoid cell total RNAs generated from affected individuals. RESULTS: Ocular phenotypes of affected members included an empty vitreous with fibrillary condensations, avascular membrane, perivascular sheathing, and progressive chorioretinal dystrophy and were similar to those of the original Wagner syndrome family. All affected eyes examined exhibited pseudoexotropia with ectopic fovea. No systemic manifestations were observed. Genetic linkage confirmed disease segregation with the previously identified WGN1 locus on 5q13-q14. A heterozygous A-->G transversion at the second base of the 3'-acceptor splice site of intron 7 (c.4004-2 A-->G) of the chondroitin sulfate proteoglycan 2 (CSPG2) gene that cosegregated with the disease was identified. Results of RT-PCR analysis indicated that the c.4004-2 A-->G mutation activates a cryptic splice site, located 39 bp downstream from the authentic 3' splice acceptor site. CONCLUSIONS: This linkage study confirmed the genetic homogeneity of the Wagner syndrome. CSPG2 encodes versican, a large chondroitin sulfate proteoglycan, which, in vitreous, binds to hyaluronan and link protein and forms large aggregates that are important for maintaining structural integrity. Although the CSPG2 gene has been excluded as a candidate for causing Wagner syndrome, these data emphasize the necessity of further mutational screening in new families and careful functional characterization.

Reduced N-acetylaspartate levels in mice lacking aralar, a brain- and muscle-type mitochondrial aspartate-glutamate carrier.

Aralar is a mitochondrial calcium-regulated aspartate-glutamate carrier mainly distributed in brain and skeletal muscle, involved in the transport of aspartate from mitochondria to cytosol, and in the transfer of cytosolic reducing equivalents into mitochondria as a member of the malate-aspartate NADH shuttle. In the present study, we describe the characteristics of aralar-deficient (Aralar-/-) mice, generated by a gene-trap method, showing no aralar mRNA and protein, and no detectable malate-aspartate shuttle activity in skeletal muscle and brain mitochondria. Aralar-/- mice were growth-retarded, exhibited generalized tremoring, and had pronounced motor coordination defects along with an impaired myelination in the central nervous system. Analysis of lipid components showed a marked decrease in the myelin lipid galactosyl cerebroside. The content of the myelin lipid precursor, N-acetylaspartate, and that of aspartate are drastically decreased in the brain of Aralar-/- mice. The defect in N-acetylaspartate production was also observed in cell extracts from primary neuronal cultures derived from Aralar-/- mouse embryos. These results show that aralar plays an important role in myelin formation by providing aspartate for the synthesis of N-acetylaspartate in neuronal cells.

Two patients with severe corneal disease in KID syndrome.

PURPOSE: To report two independent Japanese patients with keratitis, ichthyosis, and deafness (KID) syndrome and severe corneal disorder. DESIGN: Observational case reports. METHODS: Clinical observation of a 5-year-old boy (Patient 1) and a 64-year-old man (Patient 2) with KID syndrome, presenting prominent corneal diseases. Molecular genetic assessment of the GJB2 gene encoding connexin-26 was performed. RESULTS: Patient 1 had bilateral diffuse superficial punctuate keratopathy with severe corneal neovascularization. He had a missense mutation of the GJB2 gene. Patient 2 had bilateral corneal stromal keratitis and right corneal ulceration with rupture of the Descemet membrane. He did not have any pathologic mutation of the GJB2 gene. The area of palisades of Vogt was diminished and tear production reduced in both patients. Topical eye drops, and corticosteroid or antibiotics, respectively, relieved them effectively. CONCLUSION: The impaired ocular surface regulating system might be a cause of corneal disease in KID syndrome and it can be treated by eye drops.

Phylogenetic assessment of the mitochondrial DNA displacement loop haplotype in Japanese patients with Leber's hereditary optic neuropathy harboring the mitochondrial DNA G11778A mutation.

To investigate the anthropological background and the association of mitochondrial DNA (mtDNA) haplotype with the disease phenotype, the nucleotide sequence in the hypervariable segment of the displacement loop (D-loop) region of mtDNA was determined in Japanese patients with Leber's hereditary optic neuropathy (LHON) harboring the G11778A mutation. Genetic polymorphism of mtDNA was examined in 36 unrelated Japanese LHON patients who presented with bilateral optic nerve disease and had the mtDNA G11778A mutation. DNA was extracted from the peripheral blood after having obtained informed consent. The nucleotide sequence of the D-loop region (np 16,002-16,490) was directly determined. The intergenic deletion of the COII/tRNA(Lys) gene of mtDNA was also examined. From the data set of nucleotide alignments, the phylogeny of the mtDNA sequence and phenotypic diversity within the examined population were evaluated. One-base polymorphism was present at 37 different sites. The estimated value of nucleotide diversity was 0.69%. D-loop sequences were classified into 13 monophyletic clusters (CA to CM). There was not any definite ancestral haplotype of the D-loop sequence in the examined LHON population. Thus, the mutational event of G11778A appears to be independent of the evolutionary course in the D-loop haplotype. Patients with a CD plus CH cluster had a significantly older age at onset (p = 0.006), and had a family history being significantly lower as compared with patients with other clusters (p = 0.05). The mtDNA D-loop haplotype characterized by the presence of T16362C or C16290T, lacking G16129A and G16390A, may be a risk for older age at onset and other unusual clinical features in Japanese LHON patients with the G11778A mutation.