Pay attention to the detection and treatment of ocular gene therapy viral vector-associated immunity / 中华眼底病杂志

The application of gene therapy in ocular diseases is gradually expanding from mono-gene inherited diseases to multigene, multifactorial, common and chronic diseases. This emerging therapeutic approach is still in the early exploratory stage of treating diseases, and the expected benefits and risks remain highly uncertain. In the delivery process of gene therapy drugs, viral vector is currently one of the most mature and widely used vectors. The occurrence of vector-associated immunity will affect the short-term and long-term effects of gene therapy, and even cause permanent and serious damage to visual function. Therefore, gene therapy vector-associated immunity is the focus and challenge for the safety and long-term efficacy of gene therapy. During the perioperative and follow-up of gene therapy, attention should be paid to the monitoring of vector-associated immune inflammation, and appropriate measures should be taken to deal with the corresponding immune response, so as to achieve the best visual benefits for patients.

Paying attention to the natural course of disease for a development of gene therapy of inherited retinal diseases / 中华实验眼科杂志

Most inherited retinal diseases (IRDs) severely impair vision and lack effective treatments.With the approval of Luxturna, the world's first gene therapy drug for IRDs in 2017 by the U. S.FDA, gene therapy has brought new hope for the treatment of the disease.With an early onset and a relatively small number of patients, the understanding of the natural course of IRDs is limited in the past.The research on gene therapy of IRDs is mainly based on the in-depth understanding of the pathogenesis and natural course of disease, and the selection of the optimal treatment window for the implementation of gene therapy is the premise of successful treatment.At the same time, the main vector for gene therapy is recombinant virus vector, and its tissue-immunogenicity, tumorigenicity, safety of its integration with host cells and effectiveness determine the outcome of therapy, so the evaluation technology of IRDs gene therapy needs to be established.Gene therapy for ophthalmic diseases also involves the consideration of laws and regulations, ethics, product process, races and regional environment, disease progression, gene mutation types, patient benefit and risk ratio, and other factors.Therefore, it is of great significance to take full account of the differences in IRDs population, especially the particularity of children patients, and actively carry out the study on the natural course of IRDs in China for the scientific and normative development of clinical trials of gene therapy, the effective establishment of endpoint and outcome indicators for clinical studies of gene therapy, and the compliance with international norms of ethics.

Correlation analysis between benign paroxysmal positional vertigo and bone mineral density in menopausal women / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the correlation between benign paroxysmal positional vertigo (BPPV) and bone mineral density (BMD) in menopausal women with BPPV.METHODS 50 patients between the ages of 50-80 years old of menopausal women with Idiopathic benign paroxysmal positional vertigo(iBPPV)as case group,and postmenopausal healthy people of same age doing physical examinations in hospital medical examination center were selected as control group.The lumbar spine(L1-L4) and femoral neck were measured respectively using dual energy X-ray absorptiometry and expressed in T value.The case group and the control group were divided into three age groups,and the T values of three age groups were statistically analyzed.RESULTS There was significant correlation between the case group and control group(The t values are-3.68、-5.98 and-3.33,respectively,P＜0.05).Pearson correlation analysis showed that there was a negative correlation between iBPPV and bone mineral density(BMD) (r=-0.496,P＜0.05).CONCLUSION There was a correlation between benign paroxysmal positional vertigo and BMD in menopausal women.The results of this study may be helpful for the diagnosis,treatment,prognosis and precaution of iBPPV.

A recurrent mutation of CRYGD gene in a northern Chinese family with autosomal dominant congenital nuclear cataract / 中华实验眼科杂志

Background Congenital cataract is a major cause for blindness of childhood.Genetic gene mutation accounts for almost 1/3 of congenital cataract patients.The most common inheritance type is autosomal dominant congenital cataract (ADCC).Over 100 mutations in 26 genes have been found to be associated with ADCC.Objective This study was to identify the disease-causing gene mutation in a family with ADCC.Methods This study was approved by Ethic Committee of Beijing Tongren Hospital and followed Declaration of Helsinki.A northern Chinese family with autosomal dominant congenital nuclear cataract was entrolled in Beijing Tongren Hospital in January 2011.Ocular examinations were performed and periphery blood specimens were collected from each family member under the informed consent.Genomic DNA was extracted.Twenty-one microsatellite markers around 17 ADCC genes were selected for linkage analysis,and two-point LOD score was calculated.CRYGC gene and CRYGD gene were amplified and screened for mutations using direct sequencing.ProtScale software was used to analyze the changes of hydrophobicity of the mutated protein.Co-segregation of the observed change with the disease phenotype was further detected by restriction fragment length polymorphism (RFLP).Results This family included 20 members of 4 generations,and 9 patients were examined in serial 4 passages,which conformed to autosomal dominant inheritance pattern.Clinical examination revealed binocular congenital nuclear cataract in the 9 patients.Maximum two-point LOD score was 4.68 at marker D2S325 (θ=0).A known T→C change at position 127 of cDNA sequence was found by mutations screening of CRYGD gene.ProtScale programs showed an obvious increase of the local hydrophobicity in the mutant protein.RFLP results indicated that this missense mutation co-segregated with affected members of the family,but was absent in unaffected members and 100 unrelated controls.Conclusions c.T127C mutation of CRYGD gene appears to be the molecular pathogenesis of this ADCC family.Aberrant structure of mutant CRYGD protein caused by hydrophobicity change may lead to opacification of lens.