Treating Severe Adverse Drug Reactions Caused by Ischemic Optic Neuropathy with Ginkgo Biloba Extract Injection: A Case Report.

Background: Ginkgo biloba extract preparations are commonly used in ophthalmology to improve circulatory disorders and provide neurotrophic support for the treatment of optic neuropathy. However, their use also carries a higher risk of adverse drug reactions (ADRs), some of which can be severe and even life-threatening, such as anaphylactic shock. This case report highlights the importance of recognizing and managing ADRs associated with ginkgo biloba extract in ophthalmology clinical practice. This report aims to emphasize the need for appropriate patient selection, adherence to prescribing guidelines, and proactive measures to reduce ADR occurrence. Case Presentation: We present the case of a patient who experienced a severe ADR following the administration of Ginkgo biloba and Damo injection. The patient, a middle-aged individual without a history of allergies, developed anaphylactic shock within 30 minutes of medication initiation. Prompt medical intervention, including medication withdrawal, resuscitation, and intensive care unit transfer, led to symptom relief and successful recovery. Conclusions: This case underscores the need for vigilance when prescribing ginkgo biloba extract, particularly in middle-aged and elderly patients. Despite no previous history of allergies and adherence to the prescribed dosage, severe ADR can still occur. Close monitoring of patients within the first 30 minutes of medication administration is crucial. Furthermore, strict adherence to drug instructions, proper TCM syndrome differentiation, appropriate choice of infusion solvents, and strict control of drip rates should be considered to enhance patient safety. Other factors such as patient age, allergy history, and initial medication were also identified as important considerations in preventing ADRs. This case report emphasizes the significance of early identification, immediate withdrawal of medication, vital sign monitoring, and timely administration of anti-allergy drugs in managing ADR.

Medication Rules and Mechanism of Topical Traditional Chinese Medicine for Meibomian Gland Dysfunction-Related Dry Eye Disease.

Objective: To summarize the use of traditional Chinese medicine in the treatment of meibomian gland dysfunction-related dry eye disease through data mining. Additionally, it aims to explore the signaling pathways and mechanisms of critical drugs used in the treatment of this condition through network pharmacology analysis. Methods: Clinical trial literature on the topical application of traditional Chinese medicine for meibomian gland dysfunction-related dry eye disease in the past 20 years was collected from Chinese academic databases (Zhiwang, Wanfang Data, and Weipu). Association rule analysis and clustering analysis were performed using IBM SPSS. Active ingredients and target sites of critical drugs were obtained from the TCSMP and BATMAN-TCM databases. Disease target sites were sourced from databases such as DrugBank and OMIM. The drug-disease intersecting target genes were used to construct a protein-protein interaction (PPI) network in the String database. Common target genes were subjected to GO function and KEGG signaling pathway enrichment analyses using the DAVID platform. The molecular docking of active ingredients and key targets was validated using AutoDock Vina (1.1.2). Results: A total of 93 Chinese herbal medicines in 56 prescriptions were collected. The critical drugs identified were flos chrysanthemi, flos lonicerae japonicae, fructus forsythiae, radix scrophulariae, radix rehmanniae recens, and radix ophiopogonis. There were 63 active ingredients and 905 potential targets. Key targets identified through PPI analysis included AKT1, TP53, TNF, EGFR, IL6, VEGFA, IL1B, INS, EGF, and CXCL8. GO function analysis revealed processes such as positive regulation of expression, positive regulation of cell proliferation, negative regulation of apoptosis, and inflammatory reactions. The main signaling pathways identified were the MAPK signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, and cytokine-cytokine receptor interactions. Molecular docking indicated relatively strong binding activity between the small molecules of the active ingredients and the target proteins. Conclusions: The critical drugs analyzed in this study potentially exert therapeutic effects on meibomian gland dysfunction-related dry eye disease by regulating related biological processes such as anti-inflammation and repairing the corneal epithelial barrier. These findings provide a theoretical basis for future research and development of new drugs and subsequent experimental investigations.

Optic nerve injury models under varying forces.

PURPOSE: To explore the pathological changes in optic nerve injury models under varying forces. METHODS: The rats were classified into 4 groups: sham operation (SH), 0.1, 0.3, and 0.5 N. Modeling was performed using the lateral optic nerve pulling method. Seven days after modeling, Brn3a immunofluorescence was used to detect retinal ganglion cell (RGC) number, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to detect RGC apoptosis, and flash visual evoked potential (FVEP) was used to detect the optic nerve function on days 1, 3, and 7 after modeling. In addition, LC3 II and P62 expression levels in retinal tissues were detected by western blotting to observe the changes in autophagy levels. RESULTS: RGC number decreased 7 d after modeling, and it showed a downward trend with increasing damaging force. The number of apoptotic RGCs in ganglion cell layer in the 0.3 and 0.5 N groups was increased and was higher than that in the 0.1 N group. The difference in FVEP of rats in each group was mainly reflected in the P2 peak latency. LC3 II and P62 expression levels in retinal tissue of 0.3 and 0.5 N groups were higher than those of the SH and 0.1 groups; however, the difference between the 0.1 N and SH groups was not statistically significant. CONCLUSION: Precisely controlling the force of the optic nerve clamping injury model is necessary because different forces acting on the optic nerve will lead to differences in the loss of optic neurons, the conduction function of the optic nerve, and autophagy level in retinal tissues.

[A novel mutation T8821G in mitochondrial DNA may be associated with Leber's hereditary optic neuropathy].

OBJECTIVE: To report on clinical, genetic and molecular characterization of two Chinese families with Leber's hereditary optic neuropathy. METHODS: Ophthalmological examinations have revealed variable severity and age at onset of visual loss among the probands and other matrilineal relatives of both families. The entire mitochondrial genome of the two probands was amplified with PCR in 24 overlapping fragments using sets of oligonucleotide primers. RESULTS: The ophthalmological examinations showed that penetrance was 12.5% and 30.0% respectively in the two families. Sequence analysis of the complete mitochondrial genomes in these pedigrees has identified unreported homoplasmic T8821G mutation in the ATPase 6 gene and distinct sets of polymorphisms belonging to haplogroups M10a. The T8821G mutation has occurred at the extremely conserved nucleotide (conventional position 99) of the ATPase6. Thus, this mutation may alter structural formation of ATPase6, thereby leading to failure in the synthesis of ATP involved in visual impairment. CONCLUSION: Above observations have suggested that the ATPase6 T8821G mutation may be involved in the pathogenesis of optic neuropathy in these families.

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.

[The analysis of mitochondrial DNA haplogroups and variants for Leber's hereditary optic neuropathy in Chinese families carrying the m.14484T >C mutation].

The m.14484T>C mutation in mitochondrial ND6 gene (MT-ND6) is a primary mutation underlying the development of Leber's hereditary optic neuropathy (LHON) , but by itself not enough to cause visual loss. To explore the role of mitochondrial haplogroups on the expression of LHON for the people carrying the m.14484T>C mutation, we performed systematic and extended mutational screening of MT-ND6 gene in a cohort of 1177 Han Chinese patients with LHON. A total of 67 affected subjects carried the homoplasmic m.14484T>C mutation, accounting for 5.7% of this LHON population. The penetrances of optic neuropathy among 51 pedigrees carrying the m.14484T>C mutation ranged from 5.6% to 100.0%, with the average of 21.5%. The sequence analysis of entire mitochondrial genomes of 51 probands exhibited distinct sets of polymorphisms belonging to 18 Eastern Asian haplogroups. The frequencies of haplogroup A and haplogroup F were sig-nificantly less in the LHON mtDNA samples than those in 106 Chinese controls. On the other hand, the haplogroup M10a accounted for 9.8% of the patient's mtDNA samples but was absent in 106 Chinese controls. Strikingly, the average pene-trance (46.13%) of optic neuropathy for the pedigrees carrying mitochondrial haplogroup M10a was higher than those car-rying other mtDNA haplogroups. These observations indicated that mitochondrial haplogroup M10a may increase the risk of visual loss.

Effects of acupuncture on age-related macular degeneration: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: In recent years, an increasing number of patients with age-related macular degeneration (AMD) have received acupuncture treatment, but there has been no systematic review to evaluate the effect of acupuncture on patients with AMD. PURPOSE: This meta-analysis aims to review the clinical efficacy of acupuncture in the treatment of AMD. METHODS: Randomized controlled trials up to September 4, 2022 were searched in the following databases: PubMed, Ovid Medline, Embase, Cochrane Library, The Chinese National Knowledge Infrastructure Database, VIP, Wanfang, and SINOMED. Two reviewers independently performed literature screening and data extraction. RevMan 5.4 was used for the meta-analysis. RESULTS: Nine of the 226 articles were finally included. A total of 508 AMD patients (631 eyes) were enrolled, including 360 dry eyes and 271 wet eyes. The results showed that acupuncture alone or as an adjunct therapy improved both the clinical efficacy and best-corrected visual acuity (BCVA) of AMD patients and reduced their central macular thickness. The certainty of the evidence ranged from "low" to "very low". CONCLUSION: There is no high-quality evidence that acupuncture is effective in treating patients with AMD; patients with dry AMD may benefit from acupuncture treatment. Considering the potential of acupuncture treatment for AMD, it is necessary to conduct a rigorously designed randomized controlled trials to verify its efficacy.

[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.

Analysis of the Cytokine Expression in the Aqueous Humor of Individuals with BRVO-Associated Macular Edema.

Purpose: This study aimed to determine the expression levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in the aqueous humor of patients with macular edema (ME) caused by branch retinal vein occlusion (BRVO), as well as to investigate the relationship between the cytokines as mentioned earlier and best-corrected visual acuity (BCVA), ME, and the degree of ME from the molecular level. Methods: In a prospective observational study, fluorescein fundus angiography (FFA) and optical coherence tomography (OCT) were used to classify 58 patients with non-ischemic BRVO-ME into three groups according to the degree of ME: 14-mild, 17-moderate, and 27-severe. The specific concentration of IL-6, VEGF, ICAM-1, and VCAM-1 in the aqueous humor was detected using the BD CSCanto™ II Flow Cytometer (US). Spearman or Pearson correlation analysis was used to test the correlation between the levels of BCVA and severity of ME and the expression levels of IL-6, VEGF, ICAM-1, and VCAM-1 in the aqueous humor. Results: According to the obtained data, BCVA did not correlate with the severity of ME, and these four cytokines expression levels in patients' aqueous humor (P > 0.05). Moreover, BCVA did not correlate with mild, moderate, or severe ME as well (P > 0.05). However, the levels of these four cytokines were correlated with the severity of the ME. These underlined cytokines were linked to the mild, moderate, and severe degrees of ME. VEGF was also significantly correlated (r > 0.8, P < 0.0001) with the severity of ME. Conclusions: This study suggests that the severity of ME in BRVO-ME patients is significantly correlated with the expression levels of IL-6, VEGF, ICAM-1, and VCAM-1 in the aqueous humor. Lowering the level of disease-associated cytokines may potentially reduce the degree of ME. Therefore, an in-depth study of the levels and the relationship may provide some evidence for the pathogenesis, treatment, and prevention of BRVO-ME.

[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.

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 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.

[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.

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.

[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.

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.

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.

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.