Comparison of glaucomatous from non-glaucomatous optic neuropathy using Bruch’s membrane opening minimum rim width optical coherence tomography measurements

Purpose: To compare glaucomatous from non?glaucomatous optic atrophy using optical coherence tomography (OCT) based on the measurement values of Bruch’s membrane opening minimum rim width (BMO?MRW), which is a difficult task otherwise due to their varied course of disease progression, treatment protocols, and systemic association to visual impairment. Methods: This study was conducted in 40 eyes, comprising 20 eyes with non?glaucomatous optic neuropathy (NGON) and 20 eyes with glaucomatous optic neuropathy (GON). All patients underwent a complete ophthalmic examination followed by an OCT optic disc scan to calculate the measurement of BMO?MRW. Results: The 5?fold cross?validated area under the curve for GON versus NGON from logistic regression models was 0.95 (95% confidence interval [CI]: 0.86–1.00) using BMO?MRW values from all sectors. The results revealed that the measurements were significantly lesser in GON than in NGON patients. Conclusion: Hence, OCT?based BMO?MRW values could be used as an additional test to compare glaucomatous with non?glaucomatous optic neuropathy patients, especially in cases of high clinical suspicion.

SSBP1 mutation-induced autosomal dominant optic atrophy with chronic renal insufficiency: a case report and literature review / 中华实用儿科临床杂志

The data of a patient with autosomal dominant optic atrophy (ADOA) and chronic renal insufficiency caused by SSBP1 gene mutation in the Children′s Hospital Affiliated to Zhengzhou University in July 2021 was analyzed retrospectively.Literature was reviewed.The patient was a 10-year-old girl, who visited the hospital due to " growth retardation for the past 3 years and elevated serum creatinine (Scr) for the past 2 years" . On admission, the patient′s height was 130 cm (<10 th percentile of the same sex of healthy age) and her weight was 22 kg (<3 rd precentile of the same sex of healthy age). Lab examination showed that the level of blood urea nitrogen (BUN) was 16.3 mmol/L, Scr was 115.4 μmol/L, and the estimated glomerular filtration rate was 41 mL/(min·1.73 m 2). The patient was complicated with metabolic acidosis and mild anemia.Imaging findings showed small volume of both kidneys, increased background parenchymal enhancement, scattered spot-like hyperechoes and unclear boundary between the cortex and medulla.Additionally, the patient had a history of optic atrophy.Both the father and mother of the patient had no related phenotypes.The genetic test of the patient showed that c. 320G>A (p.R107Q) was a heterozygous missense mutation, which was spontaneous.A total of 5 English papers were retrieved.There were 8 kinds of SSBP1 gene mutations reported, including 7 heterozygous missense mutations [c.320G>A (p.Arg107Gln), c.119G>T (p.Gly40Val), c.331G>C (p.Glu111Gln), c.184A>G (p.Asn62Asp), c.113G>A (p.Arg38Gln), c.422G>A (p.Ser141Asn), c.79G>A (p.Glu27Lys)] and 1 homozygous mutation [c.394A>G (p.Ile132Val)]. Studies have established that almost all patients carrying SSBP1 mutations have manifestations of eye involvement, and that some patients are complicated with progressive deterioration of renal function, sensorineural deafness, growth retardation, and hypothyroidism.It suggests that SSBP1 gene mutation can cause ADOA.For patients with optic atrophy, whether they are complicated with hearing loss and growth retardation, renal morphology and renal function evaluation are recommended.Early genetic examination is helpful for diagnosis and treatment.

Research progress of optic atrophy 1-mediated mitochondrial dynamics in skeletal system diseases / 中国修复重建外科杂志

OBJECTIVE@#To review the research progress of mitochondrial dynamics mediated by optic atrophy 1 (OPA1) in skeletal system diseases.@*METHODS@#The literatures about OPA1-mediated mitochondrial dynamics in recent years were reviewed, and the bioactive ingredients and drugs for the treatment of skeletal system diseases were summarized, which provided a new idea for the treatment of osteoarthritis.@*RESULTS@#OPA1 is a key factor involved in mitochondrial dynamics and energetics and in maintaining the stability of the mitochondrial genome. Accumulating evidence indicates that OPA1-mediated mitochondrial dynamics plays an important role in the regulation of skeletal system diseases such as osteoarthritis, osteoporosis, and osteosarcoma.@*CONCLUSION@#OPA1-mediated mitochondrial dynamics provides an important theoretical basis for the prevention and treatment of skeletal system diseases.

Principais achados em um paciente com diagnóstico de Amaurose Congênita de Leber / Main findings in a patient diagnosed with Leber's Congenital Amaurosis

RESUMO A amaurose congênita de Leber, também conhecida como neuropatia óptica hereditária de Leber, é caracterizada por uma das formas mais graves de distrofia da retina com início na infância. Os achados clássicos são deficiência visual grave e precoce, nistagmo e eletrorretinograma (ERG) anormal ou não detectável. O objetivo deste estudo é relatar um caso de um paciente com amaurose congênita de Leber com comprometimento visual desde os 6 meses de vida e acentuado declínio visual a partir dos 15 anos de idade. A realização de exames específicos para confirmar o diagnóstico é importante para o manejo e o seguimento adequado do paciente e para proporcionar melhor qualidade de vida para o mesmo.

ABSTRACT Leber Congenital Amaurosis, also known as Leber hereditary optic neuropathy, is characterized by one of the most severe forms of childhood-onset retinal dystrophy. Classic findings are severe and early visual impairment, nystagmus, and abnormal or undetectable electroretinogram. The aim of this study is to report a case of a patient with Leber Congenital Amaurosis with visual impairment since the first six months of age and marked visual decline from fifteen years of age. Performing specific tests to confirm the diagnosis is important for the proper management and follow-up of the patient and to provide them with a better quality of life.

Terapia genética de injeção intravítrea de rAAV2-ND4 para neuropatia óptica hereditária de Leber: uma revisão sistemática / rAAV2-ND4 intravitreal injection gene therapy for Leber's hereditary optic neuropathy: a systematic review

RESUMO A neuropatia óptica hereditária de Leber é uma doença mitocondrial hereditária neurodegenerativa. A taxa potencial de recuperação espontânea é controversa na literatura. A terapia genética tem sido estudada como suporte aos pacientes. O objetivo desta revisão foi avaliar qualitativamente a segurança, os efeitos adversos e a eficácia da terapia gênica disponível. Trata-se de uma revisão sistemática de artigos indexados nas bases de dados PubMed®, Biblioteca Virtual em Saúde, SciELO, Cochrane, ScienceDirect, Scopus e Lilacs no primeiro semestre de 2021. Os critérios de inclusão e filtros foram: artigos relacionados ao tema, estudos randomizados, ensaios clínicos, trabalhos em humanos, últimos 5 anos, nas línguas portuguesa, inglesa e espanhola e texto completo disponível gratuitamente. Os parâmetros de exclusão foram: artigos duplicados, fuga ao tema, artigos de revisão, trabalhos não disponíveis e que fugiam aos critérios de inclusão. O coeficiente de kappa foi 0,812. A terapia não apresentou efeitos adversos sérios em nenhum dos artigos selecionados, e os efeitos menores sofreram 100% de remissão espontânea após o tratamento. Apesar de NAbs terem sido encontrados no soro de alguns pacientes, não houve associação entre a resposta imune adaptativa e a injeção do vetor viral. O tratamento foi eficaz na melhora da acuidade e campo visual. Vários estudos confirmaram a eficácia da terapia gênica, em doses baixas e médias, na melhora da acuidade visual e também sobre os efeitos adversos comuns relacionados à altas doses. A resposta imune humoral e a variação dos NAbs no soro foi citada em mais de um artigo. A terapia foi eficaz na melhora da acuidade visual e os efeitos adversos que surgiram foram tratados facilmente. No entanto, a resposta imune humoral ainda precisa ser estudada.

ABSTRACT Leber's Hereditary Optic Neuropathy (LHON) is an inherited neurodegenerative mitochondrial disease. The potential rate of spontaneous recovery is controversial in the literature. Gene therapy has been studied to support patients. The objective of this review was to qualitatively assess the safety, adverse effects, and efficacy of available gene therapy. This is a systematic review of articles indexed in PubMed®, VHL, SciELO, Cochrane, ScienceDirect, Scopus, and Lilacs databases, in the first half of 2021. Inclusion criteria and filters were: articles related to the topic, randomized studies, clinical trials, work in humans, last 5 years, in Portuguese, English, and Spanish and full text available for free. The exclusion parameters were: duplicate articles, not related to the topic, review articles, not available works, and works that did not meet the inclusion criteria. The kappa coefficient was 0.812. The therapy had no serious adverse effects in any of the selected articles, and minor effects experienced 100% spontaneous remission after treatment. Although NAbs were found in the serum of some patients, there was no association between the adaptive immune response and the injection of the viral vector. The treatment was effective in improving acuity and visual field. Several studies have confirmed the effectiveness of gene therapy, at low and medium doses, in improving visual acuity and also on common adverse effects related to high doses. The humoral immune response and the variation in serum NAbs was cited in more than one article. The therapy was effective in improving visual acuity and the adverse effects that arose were easily treated. However, the humoral immune response still needs to be studied.

Acupuncture for glaucoma-induced optic atrophy: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture for glaucoma-induced optic atrophy.@*METHODS@#A total of 70 patients (89 affected eyes) with glaucoma-induced optic atrophy were randomized into an observation group and a control group, 35 cases in each group. The control group was given basic western medicine treatment. In the observation group, on the basis of the treatment in the control group, acupuncture was applied at main acupoints i.e. Baihui (GV 20), Shangjingming (Extra), Chengqi (ST 1), Fengchi (GB 20), Zusanli (ST 36), combined with supplementary acupoints based on syndrome differentiation, once every three days, twice a week. The treatment for 3 months was required in both groups. Before treatment, after treatment and in follow-up of 6 months after treatment, the best corrected visual acuity (BCVA), intraocular pressure (IOP), indexes of visual field (visual field index [VFI], mean deviation [MD], pattern standard deviation [PSD]) and mean thickness of retinal nerve fiber layer (RNFL) were observed in the two groups.@*RESULTS@#Compared before treatment, BCVA was decreased after treatment and in follow-up in the control group (P<0.05); in the follow-up, BCVA in the observation group was higher than that in the control group (P<0.05). On each time point before and after treatment, there was no significant difference within or between the two groups (P>0.05). After treatment and in the follow-up, the mean thickness of RNFL was larger than the control group (P<0.05).@*CONCLUSION@#On the basis of the basic western medicine treatment, acupuncture can delay the decline of vision and the thinning of retinal nerve fiber layer in patients with glaucoma-induced optic atrophy.

Novel NR2F1 variant identified by whole-exome sequencing in a patient with Bosch–Boonstra–Schaaf optic atrophy syndrome

Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is an extremely rare autosomal dominant disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, hearing loss, and optic nerve atrophy. This syndrome is caused by loss-of-function variants in the nuclear receptor subfamily 2 group F member 1 ( NR2F1 ) gene. To date, approximately 80 patients have been reported with BBSOAS. Here, we describe a 3-year-old infant with delayed development, intellectual disability, strabismus, nystagmus, and optic atrophy with well-characterized features associated with BBSOAS. Whole-exome sequencing revealed a novel heterozygous missense mutation (NM_005654.6:c.437G>A, p.Cys146Tyr) in the NR2F1 gene. This missense variant is predicted to be deleterious by the protein prediction tools (SIFT, PolyPhen-2, and MutationTaster). To the best of our knowledge, this is the first patient with BBSOAS reported from Turkey.

Idiopathic intracranial hypertension leading to bilateral optic atrophy in a patient with recent COVID-19 infection: a case report

Neurologic complications are common in patients hospitalisedwith COVID-19 infection. Most common complications are myalgias, headaches, encephalopathy and dizziness. Uncommon complications are stroke, motor and sensory deficits, seizures, ataxia and movement disorders. Multiple neuro-ophthalmological manifestations have also been reported in association with COVID-19. These complications may be the result of a range of pathophysiological mechanisms like hypoxic neuronal injury during active COVID-19 infection, RAS dysfunction, immune dysfunction and direct injury by the virus etc throughout the course of the disease. Here we reported a case of neuro-ophthalmic complication of Idiopathic intracranial hypertension (IIH) followed by bilateral optic atrophy in a middle-aged man with recent COVID-19 infection. He presented to the emergency with complaints of headache, dizziness and sudden painless bilateral diminution of vision for 3 days. His fundus examination was suggestive of bilateral papilledema, his MRI brain was normal and opening pressure of CSF was raised on lumbar puncture. His MRV was normal, there was no evidence of CSVT. He was started on steroids and acetazolamide. His headache improved but there was no improvement in visual acuity. Repeat fundus showed pale disc and MRI orbit was suggestive of bilateral optic atrophy.

Association between visual function and optic fiber layer thickness after gene therapy for Leber hereditary optic neuropathy / 中华实验眼科杂志

Objective:To investigate the association between the rehabilitation of visual function and retinal nerve fiber layer (RNFL) thickness in Leber hereditary optic neuropathy (LHON) patients receiving gene therapy for the disease.Methods:A multi-center, non-randomized, single-arm clinical trial was conducted.A total of 159 LHON patients were enrolled in Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Taihe Hospital and Ezhou Central Hospital from December 2017 to December 2018.All of the patients were administered with a single unilateral intravitreal injection (0.05 μl) of recombinant adeno-associated virus 2 carrying reduced nicotinamide adenine dinucleotide dehydrogenase subunit 4 (rAAV2-ND4) and were followed up before and 1, 3, 6 and 12 months after treatment.The best corrected visual acuity (BCVA) converted to logarithm of the minimum angle of resolution (LogMAR) unit was assessed with a standard logarithmic visual acuity chart.Perimetry indicators including visual field index (VFI) and mean deviation (MD) were measured with Humphrey Field Analyzer.RNFL thickness in the superior, inferior, temporal, nasal optic disc and the average RNFL thickness were detected with Spectralis ? HRA+ OCT.The 12-month postoperative BCVA, visual field, and RNFL thickness were taken as the primary outcomes.According to the improvement of BCVA, VFI and MD at 12 months after therapy, there were 81 vision improved eyes with injection, 62 vision unimproved eyes with injection, 65 vision improved eyes without injection, and 78 vision unimproved eyes without injection, 48 VFI improved eyes with injection, 71 VFI unimproved eyes with injection, 47 VFI improved eyes without injection, and 72 VFI unimproved eyes without injection, 52 MD improved eyes with injection, 67 MD unimproved eyes with injection, 47 MD improved eyes without injection, and 72 MD unimproved eyes without injection.The correlations between BCVA, VFI, MD and RNFL thickness were evaluated by Pearson linear correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committees of Wuhan Tongji Hospital (No.TJ-IRB20180316), Taihe Hospital (No.2017-01), Ezhou Central Hospital (No.2017-K-05) and People's Hospital of Wuhan University (No.WDRY2020-K202).Written informed consent was obtained from each patient or custodian prior to entering the study cohort. Results:Among the patients receiving rAAV-ND4 gene therapy, the 12-month postoperative BCVA (LogMAR) in the injected eyes and uninjected eyes was 1.37±0.55 and 1.29±0.59, which were significantly better than 1.70±0.41 and 1.53±0.51 before treatment (baseline), respectively ( t=4.920, 3.550; both at P<0.001).The 12-month postoperative VFI of the patients were significantly improved and the 12-month postoperative MD of the patients were significantly lowered in comparison with those at baseline in the injected eyes (both at P<0.001).Similar improvements of VFI and MD were observed in the uninjected eyes (both at P<0.01).RNFL of the patients was thinner after the therapy.In the vision improved eyes with injection, the BCVA was negatively correlated with superior, inferior, temporal, nasal and average RNFL thickness ( r=-0.362, -0.292, -0.307, -0.308; all at P<0.05).In the VFI improved eyes with injection, VFI was positively correlated with superior, inferior, nasal and average RNFL thickness ( r=0.439, 0.356, 0.294, 0.401; all at P<0.05).In the MD improved eyes with injection, MD was positively correlated with superior, inferior, nasal and average RNFL thickness ( r=0.495, 0.424, 0.377, 0.474; all at P<0.05). Conclusions:The recovery of visual function is associated with RNFL thickness after the intravitreal injection of rAAV2-ND4 in LHON eyes.Recovery of visual acuity is better in the eyes with thicker RNFL.

Effect of acupuncture on retinal and choroidal thickness in patients with optic atrophy / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture on visual acuity, intraocular pressure, visual field, retinal and choroidal thickness on optic disc and macular area in patients with optic atrophy.@*METHODS@#A total of 33 patients with optic atrophy were treated with acupuncture. Acupuncture was given at Chengqi (ST 1), Shangjingming (Extra), Qiuhou (EX-HN 7) and Fengchi (GB 20) etc., 30 min each time, once a day, for 14 days. The visual acuity, intraocular pressure, visual field indexes (mean deviation [MD], pattern standard deviation [PSD] and visual field index [VFI]), optic disc retinal nerve fiber layer thickness, macular retinal thickness and choroidal thickness of optic disc and sub-foveal were compared before and after treatment.@*RESULTS@#Compared before treatment, the visual acuity was increased (P<0.05), the MD value was decreased (P<0.05), the thickness of nerve fiber layer on the upper temporal side of optic disc was thinner (P<0.05), and the choroidal thickness of average, nasal side and lower temporal side of optic disc was increased (P<0.05). There was significant correlation between visual field MD and retinal nerve fiber layer thickness in different quadrants before and after treatment (P<0.01).@*CONCLUSION@#Acupuncture could improve visual acuity, increase choroidal thickness in part of optic disc area in patients with optic atrophy.

Skin fibroblasts derived from Leber's hereditary optic neuropathy patients present mitochondrial dysfunction / 中华眼底病杂志

Objective:To investigate the feasibility of immoribund skin fibroblast cell line derived from Leber's hereditary optic neuropathy (LHON) patients as a cell model.Methods:A basic research. Two LHON patients and 2 healthy volunteers were recruited from Department of Ophthalmology of Genetic Clinic of Henan Provincial Eye Hospital. The skin tissue of participants was obtained, and the 4 immortalized skin fibroblasts were constructed by SV40 virus infection, including 2 LHON patient cells (LHON-1 and LHON-2 cells) and 2 healthy volunteers cells (NC-1 and NC-2 cells). Mitochondrial morphology in cells was observed by electron microscope. The levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide-oxidation state (NAD +), nicotinamide adenine dinucleotide-reduction state (NADH) and adenosine triphosphate (ATP) in fibroblasts were detected. Cellular oxygen consumption was measured by seahorse mitochondrial pressure assay. Cell viability was detected using cell counting kit-8 (CCK8). One-way ANOVA was performed to compare the levels of ROS, NAD +, NADH and ATP in LHON and NC cells, as well as basal oxygen consumption, maximal oxygen consumption, ATP-coupled oxygen consumption, and cell viability. Results:Compared with NC-1 and NC-2, the number of mitochondrial crest in LHON fibroblasts was significantly reduced, indicating abnormal mitochondrial morphology. Biochemical analysis showed that ROS levels in LHON cells increased, but NAD +/NADH and ATP levels decreased, and the oxygen consumption was significantly inhibited, indicating the presence of mitochondrial damage and respiratory dysfunction. The results of CCK-8 detection showed that the survival ability of LHON-1 and LHON-2 cells was worse under stress conditions. Conclusion:Immortalized skin fibroblast cell lines from LHON patients presented mitochondrial dysfunction.

Bax inhibitor 1 inhibits vascular calcification in mice by activating optic atrophy 1 expression / 南方医科大学学报

OBJECTIVE@#To investigate the effects of Bax inhibitor 1 (BI- 1) and optic atrophy protein 1 (OPA1) on vascular calcification (VC).@*METHODS@#Mouse models of VC were established in ApoE-deficient (ApoE-/-) diabetic mice by high-fat diet feeding for 12 weeks followed by intraperitoneal injections with Nε-carboxymethyl-lysine for 16 weeks. ApoE-/- mice (control group), ApoE-/- diabetic mice (VC group), ApoE-/- diabetic mice with BI-1 overexpression (VC + BI-1TG group), and ApoE-/- diabetic mice with BI-1 overexpression and OPA1 knockout (VC+BI-1TG+OPA1-/- group) were obtained for examination of the degree of aortic calcification using von Kossa staining. The changes in calcium content in the aorta were analyzed using ELISA. The expressions of Runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein 2 (BMP-2) were detected using immunohistochemistry, and the expression of cleaved caspase-3 was determined using Western blotting. Cultured mouse aortic smooth muscle cells were treated with 10 mmol/L β-glycerophosphate for 14 days to induce calcification, and the changes in BI-1 and OPA1 protein expressions were examined using Western blotting and cell apoptosis was detected using TUNEL staining.@*RESULTS@#ApoE-/- mice with VC showed significantly decreased expressions of BI-1 and OPA1 proteins in the aorta (P=0.0044) with obviously increased calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 (P= 0.0041). Overexpression of BI-1 significantly promoted OPA1 protein expression and reduced calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 (P=0.0006). OPA1 knockdown significantly increased calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 in the aorta (P=0.0007).@*CONCLUSION@#BI-1 inhibits VC possibly by promoting the expression of OPA1, reducing calcium deposition and inhibiting osteogenic differentiation and apoptosis of the vascular smooth muscle cells.

Deficiencia visual y neurológica posterior a la disfunción del sistema de derivación ventrículoperitoneal: reporte de caso / Visual and neurological impairment post-dysfunction in the ventricle-peritoneal shunt system: A case report

Resumen | Las alteraciones visuales de origen neurológico en los niños tienen diversas causas, algunas reversibles y otras no. La hidrocefalia es una de las más comunes e importantes, ya que puede producir deficiencias permanentes. Las causas de la hidrocefalia son variadas; entre las principales está la hemorragia intraventricular, generalmente debida al sangrado de la matriz germinal, el cual es muy común en recién nacidos prematuros. Se presenta el caso clínico de una paciente prematura con parálisis cerebral infantil, hemorragia intraventricular e hidrocefalia, producto de un embarazo múltiple, que presentó atrofia óptica en la infancia secundaria a la disfunción del sistema de derivación ventrículo-peritoneal. Durante su rehabilitación y tratamiento, ha recibido sesiones de neurorrehabilitación que le han permitido mejorar su agudeza y capacidad visual. Se comparó el caso de la paciente con algunos similares para establecer las semejanzas y las diferencias entre los cuadros clínicos presentados y la importancia del tipo de tratamiento médico utilizado en el curso de recuperación de la capacidad visual.

Abstract | Neurological visual impairments in children have multiple causes, some of them reversible while others are not. Hydrocephalus is one of the most important and common ones as it can result in permanent impairment. There are multiple causes of hydrocephalus, intraventricular hemorrhage being the main one. This generally occurs when the germinal matrix bleeds and is very common in preterm newborns. We present the clinical case of a patient with cerebral palsy, intraventricular hemorrhage, and hydrocephalus as a result of a preterm multiple pregnancy who developed optic atrophy during childhood secondary to ventricle-peritoneal shunt dysfunction. During the rehabilitation and treatment period, she received neurorehabilitation sessions, which improved her visual acuity and capacity. We found similarities and differences with other cases and we confirmed the importance of the treatment chosen for the recovery of visual capacity.

Research progress of optical coherence tomography and optical coherence tomography angiography in Leber hereditary optic neuropathy / 中华眼底病杂志

Leber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease. It is clinically recognizable by painless, bilateral loss of vision, and the prognosis of vision is generally poor. In recent years, the information provided by optical coherence tomography (OCT) and OCT angiography (OCTA) has greatly improved people's understanding of LHON, and new progress has been made in the intervention and treatment of LHON. A detailed understanding of the structural changes of retina and choroid under OCT and OCTA of the natural course and after treatment of LHON, may provide reference for revealing the pathogenesis, prediction of onset time, differential diagnosis, follow-up of treatment effect and prognosis of LHON.

Progress and challenges in diagnosis and treatment of Leber's hereditary optic neuropathy / 中华眼底病杂志

Leber's hereditary optic neuropathy (LHON) is a rare hereditary optic nerve disease. At present, the understanding of its etiology and pathogenesis is relatively clear. With the emergence of new drugs such as idebenone and the possibility of gene therapy for LHON, it has brought hope for patients to recover. However, because genetic testing technology has not been widely developed in China, clinical misdiagnosis of LHON as optic neuritis still occurs from time to time. How to make timely identification and correct diagnosis of LHON still poses certain challenges for Chinese ophthalmologists. In addition, in terms of treatment, the choice of treatment methods and treatment costs in the pre-onset (gene mutation carriers) and different periods after the onset of LHON are also huge challenges for patients and their families.

Effect of the regulation of mitochondrial dynamics on renal ischemia-reperfusion injury / 器官移植

Ischemia-reperfusion injury (IRI) is one of the main causes of early graft dysfunction after renal transplantation. In China, organ transplantation has entered into the era of organ donation after citizen's death. The increased risk of cardiopulmonary resuscitation, prolonged hypoperfusion time and warm ischemia time of donors may lead to IRI of the graft, and affect the short- and long-term clinical prognosis of the recipient and graft. Under IRI and other stress conditions, the mechanism of mitochondrial dynamics, mainly manifested by dynamic regulation of mitochondrial division and fusion, exert critical effect upon the biological function of mitochondria. Cell apoptosis caused by mitochondrial injury is the key event leading to acute kidney injury, which is mainly manifested by the imbalance of the regulatory mechanism of mitochondrial dynamics. In this article, the research progress on the regulatory mechanism of mitochondrial dynamics on renal IRI was reviewed, aiming to provide reference for improving the clinical outcomes of renal transplantation.

Mitochondrial Dynamics Mediates Myocardial Energy Metabolism in Coronary Heart Disease due to Blood Stasis / 中国实验方剂学杂志

Objective:To explore the mechanism of energy changes in the three stages of the formation of coronary heart disease due to blood stasis in rat model from the perspective of mitochondrial fusion-fission dynamic changes. Method:Thirty healthy male rats were divided into the blank control group （<italic>n</italic>=6） and model group （<italic>n</italic>=24） using SPSS 21.0 simple random sampling method. The rats in the blank control group were fed an ordinary diet， while those in the model group a high-fat diet. After seven days of adaptive feeding， the rats were treated with intragastric administration of vitamin D₃ （VitD₃） at 300 000 U·kg^-1 and then at 200 000 U·kg^-1 14 d later. The high-fat diet continued for 21 d， and six rats were randomly selected as samples for the pre-stage blood stasis syndrome group， followed by model verification and sampling. The remaining rats continued to receive the high-fat diet for 30 d， and six were randomly selected and categorized into the sub-stage blood stasis syndrome group， followed by model verification and sampling. The rest of rats were classified into the heart blood stasis syndrome group. While continuing the high-fat diet， they were also treated with multipoint subcutaneous injection of isoproterenol （ISO，5 mg·kg^-1） for three consecutive days. One week later， the electrocardiogram （ECG） was recorded for determining whether the modeling was successful and the samples were taken at the same time. The changes in mitochondrial morphology and quantity were observed under a transmission electron microscope. The expression of mitochondrial dynamics-related proteins was measured by Western blot and the cellular localization of related proteins by immunofluorescence assay. Result:The levels of total cholesterol and low-density lipoprotein cholesterol in the pre-stage and sub-stage blood stasis syndrome groups were significantly increased as compared with those in the blank control group （<italic>P</italic><0.05）. The blood rheology index in the pre-stage blood stasis syndrome group was significantly elevated in contrast to that in the blank control group （<italic>P</italic><0.05）. The three-layered membrane of the aorta in the blank group was intact. However， the tunica media of the pre-stage blood stasis syndrome group began to show obvious calcification， with a small number of inflammatory cells adhering to the intima. The subintima and media smooth muscles in the sub-stage blood stasis syndrome group exhibited cavity structures. The three-layered structure of the arterial wall in the heart blood stasis syndrome group was severely damaged. The ECG of the blank control group revealed the regular appearance of P wave，regular QRS waveform （no broadening or deformity）， and no obvious ST-segment depression or elevation. The ECG of the pre-stage blood stasis syndrome group showed no obvious abnormalities as compared with that of the blank control group. In the sub-stage blood stasis syndrome group， the ECG showed an upward trend of the J point and slight ST-segment elevation， with the elevation≤0.1 mV. The ECG in the heart blood stasis syndrome group displayed significant ST-segment depression （>0.1 mV） and J point depression >0.1 mV. The mitochondria in the blank control group were normal in size and morphology， with clear and dense cristae， whereas those in the pre-stage blood stasis syndrome group were fusiform with sparse cristae. Some mitochondria in the sub-stage blood stasis syndrome group were significantly elongated， and even vacuole-like changes were present. In the heart blood stasis syndrome group， the mitochondria were ruptured. As demonstrated by comparison with the blank control group， the expression levels of mitofusin 2 （Mfn2）， dynamin-related protein 1 （Drp1）， and fission protein 1 （Fis1） in the model group were significantly up-regulated （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the pre-stage blood stasis syndrome group， the heart blood stasis syndrome group exhibited down-regulated Mfn2 （<italic>P<</italic>0.05）. Compared with the blank control group and the pre-stage blood stasis syndrome group， the sub-stage blood stasis syndrome group and the heart blood stasis syndrome group displayed down-regulated optic atrophy 1（OPA1） （<italic>P</italic><0.05，<italic>P</italic><0.01）. The Drp1 and Fis1 protein expression declined significantly in the sub-stage blood stasis syndrome group in comparison with that in the pre-stage blood stasis syndrome group （<italic>P</italic><0.05，<italic>P</italic><0.01）. The expression levels of Mfn2 and Drp1 in the heart blood stasis syndrome group were lower than those in the sub-stage blood stasis syndrome group （<italic>P<</italic>0.01）. The comparison with the blank control group showed that Mfn2 and OPA1 were extensively accumulated in mitochondria of both the pre-stage and sub-stage blood stasis syndrome groups， while the red-stained Mfn2 was significantly reduced in the heart blood stasis syndrome group. The Drp1/Fis1 fluorescence was weak in the blank group and the pre-stage blood stasis syndrome group but strong in the sub-stage blood stasis syndrome group and heart blood stasis syndrome group. Conclusion:The cardiomyocyte mitochondria dynamics changes with the change in energy demand of cardiomyocytes. Mfn2 is dominated by fusion effect in the early stage of the formation of coronary heart disease due to blood stasis. With the gradual development of this disease， Mfn2 begins to mediate mitochondrial autophagy. OPA1 plays a role in intimal fusion and cristae integrity. The decreased OPA1 expression is closely related to the accelerated progression of coronary heart disease differentiated into blood stasis syndrome. The process by which Drp1 and Fis1 separate damaged mitochondria to prepare for mitochondrial autophagy contributes to alleviating the imbalance between the energy demand and supply of human body.

Boonsta-Bosch-Schaff optic atrophy syndrome with infantile spasm: A case and literatures review / 解放军医学杂志

Objective To report a case of Boonsta-Bosch-Schaff optic atrophy syndrome (BBSOAS) with infantile spasm, its clinical features as well as diagnosis and treatment process, and review the relevant literature. Methods Retrospectively analyze the clinical data of a case of BBSOAS with infant spasm patient in the First Medical Center of PLA General Hospital, retrieve the databanks of online human Mendelian genetic database (OMIM), PubMed, CNKI and Wanfang Medical Online, explore the clinical characteristic of BBSOAS with infant spasm patients, the relationship between the phenotype - genotype, and the therapeutic effect. Results The patient was a 9-month-old boy admitted to hospital due to "intermittent convulsions for 4 months". The growth and development of the child delayed, gaze following was poor; fundus examination showed pale optic disc (atrophy, small optic disc), spasm attack, and electroencephalogram indicated hypsarrhythmia. Genetic test found de novo missense mutation in NR2F1 gene c.383G>A (p.YS128tyr), so diagnosed as BBSOAS and Infantile spasms. The spasticity was not controlled and hypsarrhythmia was still existed in electroencephalogram after adrerrmrticotropic hormone (ACTH) and a variety of antiepileptic drugs were administered. Fever occurred 2 weeks after out of hospital oral perampanel, spasms was completely controlled after the febrile retrograde. A total of 9 English references were obtained by searching multiple databases and manual screening, and a total of 46 cases of BBSOAS were found, among which 9 cases were complicated with infantile spasms. All the amino acid changes caused by NR2F1 gene mutation were located in DNA-binding domain, and optic nerve atrophy or/and hypoplasia were observed. Conclusions The new missense mutation of NR2F1 gene c.383G>A that caused BBSOAS and infantile spasm is no literature report before. In case of optic atrophy or hypoplasia associated with spasm in infants and young children, the doctor should consider the possibility of BBSOAS, and do the genetic examination if necessary. Perampanel may be a potential drug for spasm control in such children.

Preliminary study of medication rule of syndrome differentiation treatment for optic atrophy by TCM master Pin-zheng Liao based on data mining / 中草药

Objective: To dig out and analyze the medication rule of optic atrophy treatment by TCM master Pin-zheng Liao using the Traditional Chinese Medicine Inheritance Support System, and summarize and explore its potential new prescription. Methods: A total of 90 TCM prescriptions for the treatment of optic atrophy by Pin-zheng Liao were collected. Based on frequency statistics, association rule, entropy clustering method rule analysis and other data mining methods, the law and characteristics of drugs were excavated. Results: A total of 113 herbs were included in 90 prescriptions, the most frequently used Chinese herbs were Lycium barbarum, Ganoderma lucidum, etc. Tonic drugs were used the most, the medicated herbs were usually sweet and peace, the Chinese herbs which belong to the liver channel were the most in channel tropism drugs. Seventeen combinations of commonly used drugs were obtained by association rule analysis. Based on entropy clustering method rule analysis, 10 potential new prescriptions were obtained. Conclusion: TCM master Pin-zheng Liao believes that optic atrophy is closely related to liver, spleen and idney. Blood stasis and vein obstruction is the main pathogenesis of the disease. The drugs with effects of activating blood circulation and dredging the meridians, tonifying liver and kidney were recommended for the treating.