[Effect of Wei's triple nine needling on eye regulation in patients with presbyopia complicated with visual fatigue of liver depression and spleen deficiency].

OBJECTIVE: To compare the clinical efficacy between Wei's triple nine needling combined with esculin and digitalis glycosides eye drops and esculin and digitalis glycosides eye drops alone for presbyopia complicated with visual fatigue of liver depression and spleen deficiency. METHODS: Forty-six cases (92 eyes) with presbyopia complicated with visual fatigue of liver depression and spleen deficiency were randomly divided into an observation group (23 cases) and a control group (23 cases, 2 cases dropped off). The cases in the observation group were treated with Wei's triple nine needling and esculin and digitalis glycosides eye drops. The acupoints included Shangming (Extra), Chengqi (ST 1), Cuanzhu (BL 2) to Jingming (BL 1), Sizhukong (TE 23) to Taiyang (EX-HN 5), etc; the needling was given once every other day, three times a week, and the eye drops were given one drop each time, three times a day. The cases in the control group were only treated with the eye drops. Both groups were treated for 7 days as one course of treatment, and 2 courses of treatment were given. The visual fatigue core symptoms score, adjustment amplitude, adjustment lag and best average corrected visual acuity were observed in the two groups before treatment, 1 week and 2 weeks into treatment, respectively. RESULTS: Compared before treatment, the visual fatigue core symptoms scores in the two groups were decreased after 1-week and 2-week treatment (P<0.05); in the observation group, the adjustment amplitude was increased after 2-week treatment (P<0.05), while in the control group, the adjustment amplitude was increased after 1-week and 2-week treatment (P<0.05); in the observation group, the adjustment lag was decreased after 1-week and 2-week treatment (P<0.05). After 2-week treatment, the visual fatigue core symptoms score in the observation group was lower than that in the control group, and the adjustment amplitude was higher than that in the control group (P<0.05). There were no significant differences in adjustment lag and best average corrected visual acuity between the two groups after 1-week and 2-week treatment (P>0.05). CONCLUSION: Wei's triple nine needling combined with esculin and digitalis glycosides eye drops could improve the visual fatigue and eye regulation ability in patients with presbyopia complicated with visual fatigue of liver depression and spleen deficiency, and the effect is better than esculin and digitalis glycosides eye drops alone.

[Therapeutic effect of Wei's triple nine needling combined with medication on optic atrophy].

OBJECTIVE: To explore the effect of Wei 's triple nine needling on visual acuity and visual field in patients with optic atrophy. METHODS: A total of 90 patients with optic atrophy were randomized into an observation group and a control group, 45 cases in each one. Treatment of Wei 's triple nine needling combined with conventional medication were adopted in the observation group, conventional medication was given in the control group. Treatment for 4 weeks was required in both groups. Before treatment and 2, 4 weeks into treatment, the visual acuity and visual field were observed, and the clinical efficacy was evaluated in both groups. RESULTS: The total effective rate was 57.8% (26/45) in the observation group, which was superior to 28.9% (13/45) in the control group (P<0.05). After 2-week and 4-week treatment, the visual acuity was improved (P<0.01), the mean defect (MD) of visual field was decreased (P<0.01), the mean sensitivity (MS) of visual field was increased in the observation group (P<0.05, P<0.01). After 2-week and 4-week treatment, the visual acuity and the MD of visual field were improved (P<0.01, P<0.05), while the difference of MS of visual field compared before treatment had no statistical significance in the control group (P>0.05). The improvement of visual acuity, MD and MS of visual field after 2-week and 4-week into treatment in the observation group were superior to those in the control group (P<0.05, P<0.01). CONCLUSION: Wei 's triple nine needling can effectively improve the visual acuity and the defect of visual field in patients with optic atrophy.

[Acupuncture prescription of "Wei's triple nine needling therapy" in the treatment of optic nerve disease].

"Wei 's triple nine needling therapy" is the crucial acupuncture prescription in treatment of eye diseases in Wei 's academic school of ophthalmology. "Wei 's triple nine needling therapy" includes the three points near to the eyes, the three groups of points for penetrating acupuncture around the eyes and the acupoint selection based on the general differentiation of syndrome. In this paper, the acupoint selection and the thinking of acupoint combination were introduced in the treatment of optic nerve disease on the base of the theory of "Wei 's triple nine needling" prescription. The specific needling manipulations at different regions involved in the triple needling procedure were explained in detail. It is proposed that the acupoints are combined and the correct needling manipulations selected rationally in compliance with the illness condition and the syndrome characteristics to ensure maximally the clinical effects of "Wei 's triple nine needling therapy".

Acupuncture and herbal formulation compared with artificial tears alone: evaluation of dry eye symptoms and associated tests in randomised clinical trial.

OBJECTIVE: Dry eye is a common disease with great health burden and no satisfactory treatment. Traditional Chinese medicine, an increasingly popular form of complementary medicine, has been used to treat dry eye but studies have been inconclusive. To address this issue, we conducted a randomised investigator-masked study which included the robust assessment of disease mechanisms. METHODS AND ANALYSIS: Eligible participants (total 150) were treated with artificial tear (AT) alone, with added eight sessions of acupuncture (AC) or additional daily oral herb (HB) over a month. RESULTS: Participants treated with AC were more likely to respond symptomatically than those on AT (88% vs 72%, p=0.039) with a difference of 16% (95% CI: 0.18 to 31.1). The number-to-treat with AC to achieve response in one person was 7 (3 to 157). Participants in the AC group also had reduced conjunctival redness (automatic grading with Oculus keratograph) compared with AT (p=0.043) and reduced tear T helper cell (Th1)-cytokine tumour necrosis factor α (p=0.027) and Th2-cytokine interleukin 4 concentrations (p=0.038). AC was not significantly superior to AT in other outcomes such as tear osmolarity, tear evaporation rates, corneal staining and tear break-up times. No significant adverse effects were encountered. HB was not significantly different in the primary outcome from AT (80% vs 72%, p=0.26). CONCLUSIONS: AC is safe and provides additional benefit in mild to moderate dry eye up to 1 month, compared with ATs alone. Treatment is associated with demonstrable molecular evidence of reduced inflammation. Provided that suitably qualified practitioners are available to implement standardised treatment, AC may be recommended as adjunctive therapy to AT. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT02219204)registered on 14 August 2014.

Leber's hereditary optic neuropathy is potentially associated with a novel m.5587T>C mutation in two pedigrees.

Mitochondrial (mt)DNA mutations have been revealed to be associated with Leber's hereditary optic neuropathy (LHON). The present study conducted clinical, genetic and molecular evaluations of two Han Chinese families. A total of 4 (3 men and 1 female) out of 14 matrilineal relatives in the families exhibited visual impairment with variable severity and age of onset. The average age of onset of visual loss was 20.5 years old. Molecular analysis of the complete mitochondrial genome in these pedigrees demonstrated that the three primary mutations associated with LHON were not detected; however, the homoplasmic m.5587T>C mutation was identified, which was localized at the end of the mitochondrially encoded transfer (t)RNA alanine gene and may alter the tertiary structure of this tRNA. Subsequently, this structural alteration may result in tRNA metabolism failure. In addition, distinct sets of mtDNA polymorphisms belonging to haplogroup F1 were detected in both families tested. The findings of the present study suggested that the m.5587T>C mutation may be involved in the pathogenesis of visual impairment. In addition, the mtDNA variant m.15024G>A(p.C93H) in the mitochondrially encoded cytochrome B gene was detected in both families, which exhibited evolutionary conservation, indicating it may serve a potential modifying role in the development of visual impairment associated with m.5587T>C mutation in these families. Furthermore, other modifying factors, including nuclear modifier genes, and environmental and personal factors may also contribute to the development of LHON in subjects carrying this mutation.

Mitochondrial haplogroup D4j specific variant m.11696G > a(MT-ND4) may increase the penetrance and expressivity of the LHON-associated m.11778G > a mutation in Chinese pedigrees.

Leber's hereditary optic neuropathy (LHON) is one of the most common mitochondrial disorders. We report here the clinical, genetic and molecular analysis of mitochondrial DNA (mtDNA) in eight Han Chinese families carrying the known mitochondrial 11778G > A(MT-ND4) mutation. Thirty-seven (26 males/11 females) of 77 matrilineal relatives in these families exhibited the variable severity and age-at-onset of optic neuropathy. The penetrances were from 25% to 75%, with the average of 42%, and the age-at-onset for visual impairment varied from 10 to 25 years, with the average of 17 in these Chinese pedigrees. Molecular analysis of their mtDNA identified distinct sets of variants belonging to the Eastern Asian haplogroupD4j. Except the known m.11778G > A mutation, the m.11696G > A(MT-ND4) mutation caused the substitution of an isoleucine for valineat amino acid position 313, located in a predicted transmembrane region of ND4. And, it is reported that the m.11696G > A mutation was associated with LHON, and appeared to contribute to higher penetrance in these nine Chinese families than other Chinese families carrying only the m.11778G > A mutation. Therefore, the mitochondrial haplogroup D4j specific m.11696G > A mutation may act in synergy with the primary LHON-associated m.11778G > A mutation, thereby increasing the penetrance and expressivity of visual loss in these Chinese families.

Leber's hereditary optic neuropathy caused by the homoplasmic ND1 m.3635G>A mutation in nine Han Chinese families.

In this report, we investigated the molecular mechanism underlying Leber's hereditary optic neuropathy (LHON)-associated mitochondrial m.3635G>A (p.S110N, ND1) mutation. A mutational screening of ND1 gene in a cohort of 1070 Han Chinese subjects LHON identified the m.3635G>A mutation in nine Chinese families with suggestively maternally transmitted LHON. Thirty-eight (22 males/16 females) of 162 matrilineal relatives in these families exhibited the variable severity and age-at-onset of optic neuropathy. Molecular analysis of their mitochondrial genomes identified the homoplasmic m.3635G>A mutation and distinct sets of polymorphisms belonging to the Asian haplogroups G2a1, R11a, D4, R11a, M7b2, G1a, F1a1, B4, and N9a3, respectively. Using cybrids constructed by transferring mitochondria from lymphoblastoid cell lines derived from one Chinese family into mtDNA-less (ρ(0)) cells, we showed ~27% decrease in the activity of NADH:ubiquinone oxidoreductase (complex I) in mutant cybrids carrying the m.3635G>A mutation, compared with control cybrids. The respiratory deficiency caused by the m.3635G>A mutation results in decreased efficiency of mitochondrial ATP synthesis. These mitochondrial dysfunctions caused an increase in the production of reactive oxygen species in the mutant cybrids. The data provide the direct evidence for the m.3635G>A mutation leading to LHON. Our findings may provide new insights into the understanding of pathophysiology of LHON.

Mitochondrial haplotypes may modulate the phenotypic manifestation of the LHON-associated ND1 G3460A mutation in Chinese families.

To investigate the pathophysiology of Leber's hereditary optic neuropathy (LHON), a cohort of 1164 Han Chinese subjects with LHON were screened for ND1 G3460A mutation. A total of 295 subjects from 16 Han Chinese families carrying the G3460A mutation underwent a clinical and genetic evaluation and molecular analysis of mitochondrial (mt)DNA. The incidence of G3460A mutation was 1.4% in this cohort of Chinese subjects with LHON. Twenty-seven (20 males/7 females) of 109 matrilineal relatives among 10 Chinese pedigrees carrying this mutation exhibited a wide range of severity and age-at-onset in visual impairment. Penetrances of optic neuropathy ranged from 7.1% to 50%, with the average of 24.5%. The age-at-onset of 27 affected matrilineal relatives varied from 10 to 40 years, with the average of 22 years. Molecular analysis identified the homoplasmic G3460A mutation and distinct sets of variants belonging to eight haplogroups. Haplogroup M with G3460A mutation was of higher frequency than those in controls. The penetrances of visual loss in families carrying mitochondrial DNA haplogroups A, B and M were higher than those in other families. Furthermore, haplogroup-specific variants tRNA(Ser(AGY)) A12223G, tRNA(Thr) G15927A and tRNA(Glu) A14693G may enhance the penetrance of visual loss in these families. The G3460A mutation occurred through recurrent origins and founder events in Chinese population. Mitochondrial modifiers may modulate the penetrance and expressivity of optic neuropathy among Chinese pedigrees carrying the G3460A mutation. Thus, our findings may provide new insights into the understanding of pathophysiology and valuable information on the management of LHON.

Mitochondrial haplotypes may modulate the phenotypic manifestation of the LHON-associated m.14484T>C (MT-ND6) mutation in Chinese families.

Mitochondrial m.14484T>C (MT-ND6) mutation has been associated with Leber's hereditary optic neuropathy. Previous investigations revealed that the m.14484T>C mutation is a primary factor underlying the development of optic neuropathy but is not sufficient to produce a clinical phenotype. However, mitochondrial haplogroups have been proposed to modulate the phenotypic manifestation of the m.14484T>C mutation. Here, we performed the clinical, genetic evaluation and complete mitochondrial genome sequence analysis of 41 Han Chinese pedigrees carrying the m.14484T>C mutation. These families exhibited a wide range of penetrances and expressivities of optic neuropathy. The average ratio between affected male/female matrilineal relatives from 41 families was 2:1. The penetrance of optic neuropathy in these Chinese pedigrees ranged from 5.6% to 100%, with the average of 23.8%. Furthermore, the age-of-onset for optic neuropathy varied from 4 to 44 years, with the average of 19.3 years. Sequence analysis of their mitochondrial genomes identified distinct sets of polymorphisms belonging to ten Eastern Asian haplogroups, indicating that the m.14484T>C mutation occurred through recurrent origins and founder events. We showed that mitochondrial haplogroups M9, M10 and N9 increased the penetrance of optic neuropathy in these Chinese families. In particular, these mitochondrial haplogroup specific variants: m.3394T>C (MT-ND1), m.14502T>C (MT-ND4) and m.14693A>G (MT-TE) enhanced the penetrance of visual loss in these Chinese families. These data provided the direct evidence that mitochondrial modifiers modulate the variable penetrance and expressivity of optic neuropathy among Chinese pedigrees carrying the m.14484T>C mutation.

[The analysis of Leber's hereditary optic neuropathy associated with mitochondrial tRNAAla C5601T mutation in seven Han Chinese families].

We reported here the clinical, genetic, and molecular characterization of Leber's hereditary optic neuropathy (LHON) with C5601T mutation in seven Chinese families. The ophthalmologic examinations of seven Chinese families who were clinically diagnosed LHON were conducted. Strikingly, these families exhibited very low penetrance of visual impairment, and the penetrance was 9.5%, 14.3%, 4.5%, 8.3%, 10.0%, 22.2% and 25.0%. Meanwhile, entire mitochondrial genome of seven probands was amplified by PCR using 24 pairs of oligonucleotide primers with overlapping fragments. Molecular analysis of mitochondrial DNA (mtDNA) in these pedigrees revealed the absence of three common LHON associated G11778A, G3460A and T14484C mutations but the presence of homoplastic LHON associated tRNAAla C5601T mutation in probands and other matrilineal relatives. These mtDNA polymorphism sites belongs to the Asian haplogroups G2, G2a1, G2a1, G2, G2b, G2a1 and G2. By analyzing mitochondrial genome, seven LHON families all carry the C5601T mutation. The C5601T mutation occurs at the highly conserved nucleotide (conventional position 59) of tRNAAla, thereby contributing to the structural formation and stabilization of functional tRNAs and leading to mitochondrial dysfunction involved in visual impairment. The incomplete penetrance of visual loss in these seven Chinese pedigrees strongly indicates that the tRNAAla C5601T mutation was itself insufficient to produce a clinical phenotype. The lack of functional mtDNA variants in these pedigrees ruled out the role of mitochondrial background in the phenotypic expression of visual loss. Therefore, nuclear backgrounds and environmental factors seem to be modifying factors for the phenotypic manifestation of the tRNAAla C5601T mutation in the seven Chinese families.

[A clinical study of Leber hereditary optic neuropathy].

OBJECTIVE: To investigate the clinical characteristics of Leber hereditary optic neurology (LHON) patients with different primary site mutation. METHODS: Four hundred and fourteen patients with optic neuropathy were divided into three groups: clinically diagnosed LHON group (group A), probable LHON group (group B), optic neuropathy of unknown reason group (group C). Visual acuity (VA), colour vision, Intraocular pressure (IOP), virtual field and visual evoked potential (VEP) were tested for all the patients. Some (64 cases) had optical coherence tomography (OCT) measurement. Mutations of mtDNA were detected for all the groups, and clinical analysis were carried out emphatically in the patients with the 11778 mutation confirmed by gene assessment. T paired test was used to evaluate two group patients of different Mitochondrial DNA mutation. RESULTS: Gene mutations were found in 215 of the 414 patients (52%). Approximately 93% (199/255) of the patients were caused by the common primary mutations (11778, 14484, 3460 mutation), in which 100% mutation (106/106) in group A, 65% (91/139) in group B, and 11% (18/169) in group C. No cases were diagnosed with confirmed LHON in the patients with unilateral optic neuropathy. Fundus examination in 334 eyes of 167 cases showed pseudo papilledema (54 eyes), normal (67 eyes), pale disc or pale on the temporal side of the optic disc (213 eyes). On the basis data of OCT from 64 patients and 84 normal person, RNFL was found thickening at the early stage and thinning gradually at the later stage in the LHON patients. But, the RNFL thickness of patients with 1-2 years history was not significantly different from the patients with over 2 years history(P = 0.051), and there was no difference among the patients with different mitochondrial DNA mutations. The initial mean VA of patients with the 14484 mutation and 11778 mutation were 3.6 ± 0.65, 3.75 ± 0.54 (t = 0.536, P > 0.05), but the follow-up VA were 4.29 ± 0.55 (t = 4.034, P < 0.001) and 3.93 ± 0.49 respectively (t = 1.857, P > 0.05). CONCLUSIONS: The symptoms and fundus manifestation were similar in the LHOH patients with different primary site mutation. Gene mutation analysis is helpful to assess the prognosis of visual acuity.

Leber's hereditary optic neuropathy is associated with the T12338C mutation in mitochondrial ND5 gene in six Han Chinese families.

PURPOSE: To investigate the molecular pathogenesis of Leber's hereditary optic neuropathy (LHON) in Chinese families. DESIGN: Six Han Chinese families who seem to have maternally transmitted LHON were studied by clinical, genetic, and molecular evaluations. PARTICIPANTS: One hundred twenty-seven subjects from 6 Chinese families with a wide range of age-at-onset and severity of visual impairment. METHODS: All subjects underwent clinical examination, genetic evaluation, and molecular analysis of mitochondrial DNA (mtDNA). MAIN OUTCOME MEASURES: The ophthalmologic examinations included visual acuity, visual field examination, visual evoked potentials, and fundus photography. The mtDNA analysis included the polymerase chain reaction (PCR) amplification of entire mtDNA and subsequent sequence determination. RESULTS: Six families exhibited low penetrance of visual impairment, with an average of 10.8%. In particular, 9 (6 males/3 females) of 86 matrilineal relatives in these families exhibited variable severity and age at onset in visual dysfunction. The average age at onset of visual loss was 20 years. Molecular analysis of mtDNA in these families identified the homoplasmic ND5T12338C mutation and distinct set of variants belonging to the Asian haplogroup F2. The T12338C mutation is only present in the maternal lineage of those pedigrees and not in 178 Chinese controls. This mutation resulted in the replacement of the first amino acid, a translation-initiating methionine with a threonine, shortening 2 amino acids of ND5 polypeptide. The T12338C mutation is also located in 2 nucleotides adjacent to the 3' end of the tRNA(Leu(CUN)). Thus, this mutation may alter ND5 mRNA metabolism and the processing of RNA precursors. As a result, this mutation impairs respiratory function, leading to visual impairment. CONCLUSIONS: Several lines of evidence suggest that the mitochondrial ND5T12338C mutation is associated with LHON. The tissue specificity of this mutation is likely due to the involvement of nuclear modifier genes. The identification of nuclear modifiers is important for the elucidation of the pathogenic mechanism of LHON and an open avenue for therapeutic interventions. The T12338C mutation should be added to the list of inherited risk factors for future molecular diagnosis. Our findings are helpful for counseling families with LHON.

[Leber's hereditary optic neuropathy may be associated with the mitochondrial tRNAGlu A14693G mutation in three Chinese families].

We reported here the clinical, genetic and molecular characterization of three Han Chinese families with Leber's hereditary optic neuropathy. Ophthalmologic examinations revealed the variable severity and age-at-onset of visual loss among probands and other matrilineal relatives of these families. Strikingly, these families exhibited extremely low penetrances of visual impairment. Sequence analysis of complete mitochondrial genomes in these pedigrees identified the known homoplasmic tRNAGlu A14693G mutation and distinct sets of polymorphism belonging to haplogroups Y1b, Y1 and Y1, respectively. The A14693G mutation occurs at the extremely conserved nucleotide (conventional position 54) of tRNAGlu. Thus, this mutation may alter structural formation and stabilization of functional tRNAs, thereby leading to a failure in tRNA metabolism and mitochondrial dysfunction involved in visual impairment. However, none of other variants showed the evolutionary conservation and functional significance. These observations suggested that the tRNAGlu A14693G mutation may be involved in the pathogenesis of optic neuropathy in these families.

Very low penetrance of Leber's hereditary optic neuropathy in five Han Chinese families carrying the ND1 G3460A mutation.

We report here the clinical, genetic, and molecular characterization of five Han Chinese families with Leber's hereditary optic neuropathy (LHON). Strikingly, there were very low penetrances of visual impairment in these Chinese families, ranging from 4.2% to 22.2%, with an average of 10.2%. In particular, only 7 (4 males/3 females) of 106 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual dysfunction. The age-at-onset for visual impairment in matrilineal relatives in these families, varied from 20 to 25 years, with an average of 21.8 years old. Molecular analysis of mitochondrial genomes identified the homoplasmic ND1 G3460A mutation and distinct sets of variants, belonging to the Asian haplogroups B5b, C4a1, D5, F1, and R9, respectively. This suggests that the G3640A mutation occurred sporadically and multiplied through evolution of the mtDNA in China. However, there was the absence of known secondary LHON-associated mtDNA mutations in these Chinese families. Very low penetrance of visual loss in these five Chinese pedigrees strongly indicated that the G3640A mutation was itself insufficient to develop the optic neuropathy. The absence of secondary LHON mtDNA mutations suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the G3640A mutation in those Chinese families with low penetrance of vision loss. However, nuclear modifier genes, epigenetic and environmental factors appear to be modifier factors for the phenotypic manifestation of the G3640A mutation in these Chinese families.

Low penetrance of Leber's hereditary optic neuropathy in ten Han Chinese families carrying the ND6 T11484C mutation.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder. The purpose of this investigation is to understand the role of mitochondrial haplotypes in the development of LHON associated with ND6 T14484C mutation in Chinese families. METHODS: One hundred fourteen subjects from ten Han Chinese families with LHON were studied by the clinical and genetic evaluation as well as molecular and biochemical analyses of mitochondrial DNA (mtDNA). RESULTS: Clinical evaluation revealed that ten families exhibited extremely low penetrance of visual impairment, with an average of 10%. In particular, ten (8 males/2 females) of 114 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual dysfunction. The average age-of-onset of vision loss was 19 years old. Molecular analysis of mitochondrial DNA (mtDNA) identified the homoplasmic T14484C mutation and distinct sets of variants, belonging to the Asian haplogroups B5b, D4, D4g1b, G3a2, R11, R11a and Z3, respectively. However, there was the absence of secondary LHON-associated mtDNA mutations in these ten Chinese families. CONCLUSION: The low penetrance of vision loss in these Chinese pedigrees strongly indicated that the T14484C mutation was itself insufficient to produce a clinical phenotype. The absence of secondary LHON mtDNA mutations suggests that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the T14484C mutation in those Chinese families with low penentrace of vision loss. However, nuclear modifier genes and environmental factors appear to be modifier factors for the phenotypic manifestation of the T14484C mutation in these Chinese families.

Leber's hereditary optic neuropathy is associated with mitochondrial ND6 T14502C mutation.

We report here the clinical, genetic, and molecular characterization of three Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age of onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T14502C (I58V) mutation, which localized at a highly conserved isoleucine at position 58 of ND6, and distinct sets of mtDNA polymorphisms belonging to haplogroups M10a, F1a1, and H2. The occurrence of T14502C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Here, mtDNA variants I187T in the ND1, A122V in CO1, S99A in the A6, and V254I in CO3 exhibited an evolutionary conservation, indicating a potential modifying role in the development of visual impairment associated with T14502C mutation in those families. Furthermore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic manifestation of the LHON-associated T14502C mutation in these Chinese families.

Leber's hereditary optic neuropathy is associated with mitochondrial ND1 T3394C mutation.

We report here the clinical, genetic and molecular characterization of four Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age-of-onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T3394C (Y30H) mutation, which localized at a highly conserved tyrosine at position 30 of ND1, and distinct sets of mtDNA polymorphisms belonging to haplogroups D4b and M9a. The occurrence of T3394C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. However, there was the absence of functionally significant mtDNA mutations in these four Chinese pedigrees carrying the T3394C mutation. Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated T3394C mutation.

Extremely low penetrance of Leber's hereditary optic neuropathy in 8 Han Chinese families carrying the ND4 G11778A mutation.

PURPOSE: To investigate the role of mitochondrial haplotypes in the development of Leber's hereditary optic neuropathy (LHON) associated with the ND4 G11778A mutation in Chinese families. DESIGN: Eight Han Chinese families with maternally transmitted LHON were studied using clinical, genetic, and molecular evaluations. PARTICIPANTS: One hundred sixty-seven subjects from 8 Chinese families with a wide age range and severity of visual impairment. METHODS: All subjects underwent the clinical and genetic evaluation, as well as molecular analysis of mitochondrial DNA (mtDNA). MAIN OUTCOME MEASURES: The ophthalmologic examinations included visual acuity, visual field examination, visual evoked potentials, and fundus photography. Mitochondrial DNA analysis included the polymerase chain reaction amplification of the entire mtDNA and subsequent sequence determination. RESULTS: Eight families exhibited extremely low penetrance of visual impairment, with the average of 13%. In particular, 14 (12 males and 2 females) of 119 matrilineal relatives in these families exhibited the variable severity and age at onset in visual dysfunction. The average age of onset of vision loss was 17 years. Molecular analysis of mtDNA identified the homoplasimic ND4 G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M8a2, D4g2, B4a1c, B5b, N9a1, D4b2b, C, and M7b1. However, there was an absence of secondary LHON-associated mtDNA mutations in these 8 Chinese families. CONCLUSIONS: The extremely low penetrance of vision loss in these 8 Chinese pedigrees strongly indicates that the G11778A mutation was itself insufficient to produce a clinical phenotype. The absence of secondary LHON mtDNA mutations suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the G11778A mutation in those Chinese families with very low penentrace of vision loss. However, nuclear backgrounds and environmental factors seem to be modifying factors for the phenotypic manifestation of the G11778A mutation in these Chinese families.

[To improve understanding of etiology of optic neuritis in China].

Domestic ophthalmologists have different understandings on the causes of optic neuritis. Some of them consider infection is the main cause, some believe that so-called idiopathic optic neuritis caused by central nervous system primary demyelinating disease, such as multiple sclerosis is the most common type of optic neuritis, while others suggest that optic neuritis is attributed to autoimmune disease. Based on the review of literatures, we describe the development of definition and etiology of optic neuritis in Western countries and in China, and then provide some suggestion to a better understanding of etiology of optic neuritis in China. We also expect to have a population-based, multiple-center study to provide more extensive and accurate data on the etiology of optic neuritis in China.