Epigenetic modifications such as DNA methylation, histone post-translational modifications, non-coding RNA are reversible, heritable alterations which are induced by environmental stimuli. Major risk factors of diabetes and diabetic complications including hyperglycemia, oxidative stress and advanced glycation end products, can lead to abnormal epigenetic modifications in retinal vascular endothelial cells and retinal pigment epithelium cells. Epigenetic mechanisms are involved in the pathogenesis of macular edema and neovascularization of diabetic retinopathy (DR), as well as diabetic metabolic memory. The heritable nature of epigenetic marks also playsakey role in familial diabetes mellitus. Further elucidation of epigenetic mechanisms in DR can open the way for the discovery of novel therapeutic targets to prevent DR progression.
ObjectiveTo investigate the association of high density lipoprotein cholesterol (HDL-C) and cholesterol ester transfer protein (CETP) TaqIB mutation with non-arteritic anterior ischemic optic neuropathy (NA-AION) in the Shaanxi Han ethnic population. MethodsThe study cohort consisted of 45 individuals that had been diagnosed with NA-AION and 45 healthy controls (matched for age, gender). None of the cases or controls had a history of diabetes, serious cardio-cerebral vascular diseases, liver and kidney dysfunction that might influence plasma lipid levels. Plasma HDL-C was detected by enzyme-linked immunosorbent one-step, through the Toshiba TBA-40FR automatic biochemical analyzer. CETP TaqIB gene polymorphism was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques for analysis. B2B2 genotype was only a fluorescence band with 535 bp; B1B1 genotype was 2 fluorescence bands with 361, 174 bp; B1B2 genotype was 3 fluorescence bands with 535, 361, 174 bp. The relative risk of genotype, HDL-C and disease occurrence was analyzed by logistics regression analysis. ResultsThere have no significant difference between NA-AION patients and controls about plasma total cholesterol level and triglyceride level (t=1.907, 1.877; P > 0.05). The plasma HDL-C levels were significantly lower in NA-AION patients than in controls (t=2.367, P=0.022). Compared with controls, the prevalence of B1B1 genotype and B1 allele was higher (χ2=17.289, P=0.001), the prevalence of B2 allele (χ2=15.648, P=0.000) was lower in NA-AION patients. The lower concentration of HDL-C was risk factor of NA-AION (odds ratio=6.143, 95% confidence interval 1.262-29.895, χ2=27.676;P=0.013). The proportion of B1B1 genotype was significantly higher in NA-AION patients than in controls (odds ratio=2.24, 95% confidence interval 2.427-36.323, χ2=10.526; P=0.001). ConclusionsThe low plasma HDL-C is independent risk factor for NA-AION and is associated with the development of NA-AION in the Shaanxi Han ethnic population. CETP TaqIB mutation is associated with low plasma HDL-C in NA-AION in the Shaanxi Han ethnic population.
Objective To investigate the polymorphism of the vitamin D receptor gene (VDR)TaqⅠin relation to diabetic retinopathy. Method Fragment length discrepant allele specific PCR(FLDAS-PCR) were used to determine VDR genetypes in 158 patients with diabetic retinopathy and in 198 normal subjects. Results The frequency distribution of VDR genotypes in diabetic retinopathy patients was 106 (67.1%) in TT, 33(20.9%) in Tt, 19(12.0%) in tt; and in normal persons was 165 (83.3%) in TT, 23(11.6%) in Tt, 10 (5.1%) in tt. There was a significant difference between diabetic retinopathy patients and normal persons in distribution of VDR gene TaqⅠgenotypes(Plt;0.05). Conclusions There is some distribution alterations of VDR gene polymorphism in diabetic retinopathy patients. (Chin J Ocul Fundus Dis, 2006, 22: 94-96)
Familial exudative vitreoretinopathy (FEVR) is a rare inherited disorder of retinal angiogenesis, including autosomal dominant, autosomal recessive, or X-linked forms. Zinc finger protein 408 (ZNF408) was recently found to be associated with FEVR. Cell transfection showed that it was a dominant negative regulator of FEVR pathogenesis. Knocking down ZNF408 in zebrafish by antisense morpholino oligonucleotides indicated it involved in retinal blood vessel development. Understanding the protein structure, gene localization, basic functions and the role of ZNF408 in retinal development will contribute to uncover the pathogenesis of FEVR.
Objective To explore and implement a systematic, case guided online interactive training course for neurologists to improve their diagnosis and treatment of rare genetic diseases. Methods Doctors who participated in the course investigation of the neurogenetic project of the Department of Neurology of Peking Union Medical College Hospital between January and September 2021 were selected. Based on andragogy theory, a genetics training course for neurologists was developed by applying Kern’s six steps of curriculum development. According to the time of participating in the doctor’s courses, they were divided into three groups: completed all courses (10.7 h group), completed more than 1/2 courses (5.3～10.7 h group) and completed less than 1/2 courses (<5.3 h). According to the length of service, they were divided into groups of less than 10 years, 10-20 years and more than 20 years. Analyze the benefit difference of different doctors’ training time, and collect their feedback scales on the curriculum for the improvement of follow-up courses. Results A total of 54 doctors were included. Among them, 17 (31.5%) completed all courses, 29 (53.7%) completed more than 1/2 courses, and 8 (14.8%) completed less than 1/2 courses. There was a statistically significant difference among the three groups in the self-assessment improvement score (H=12.341, P=0.002). The results of pairwise comparison between groups of self-assessment improvement score showed that the <5.3 h group was lower than that of the 10.7 h group (P=0.007), and the the <5.3 h group was also lower than that of the 5.3～10.7 h group (P=0.002). 33 (61.1%) in the less than 10 years group, 16 (29.6%) in the 10-20 years group, and 5 (9.3%) in the more than 20 years group. There was no correlation between participating in work and course time (rs=0.113, P=0.418). 54 (100.0%) believed that they had more than moderate help (≥3 points). Most doctors (>90%) had a good evaluation of the curriculum. Conclusion The periodic neurogenetic re-education project is helpful for clinical diagnosis and treatment of rare neurogenetic diseases.
Objective To determine the association of -429T/C and G1704T polymorphisms in the receptor for advanced glycation end products gene with proliferative diabetic retinopathy (PDR). Methods Case-control study. From the Beijing Desheng Diabetic Eye Study cohort of 1467 patients with type 2 diabetes mellitus (T2DM),atotal of 97 patients with PDR and 105 diabetic patients without retinopathy (DWR, duration of diabetes 15 years) were included for this study. Questionnaires were collected and general ophthalmologic examinations were performed. Biochemical analysis was conducted. DNA was extracted from peripheral venous blood. The -429T/C and G1704T single nucleotide polymorphisms were detected by the means of PCR-restrication fragment length polymorphisms. Results The frequency distribution of -429T/C in DWR group was 81.0% in TT, 16.1% in TC, 2.9% in CC. The frequency distribution of -429T/C in PDR group was 77.3% in TT, 20.6% in TC, 2.1% in CC. There was no significant statistical difference between the two groups (χ2=0.40, P > 0.05). Frequency of the -429T/C minor alleleCin the DWR and PDR group were 11.0% and 12.4%, respectively, with no significant statistical difference between the two groups (χ2=0.20，P > 0.05). The frequency distribution of G1704T in DWR group was 66.7% in GG, 29.5% in GT, 3.8% in TT. The frequency distribution of G1704T in PDR group was 78.4% in GG, 21.6% in GT. There was no significant statistical difference between the two groups (χ2=3.44, P > 0.05). Frequency of the G1704T minor alleleTin the DWR and PDR group were 18.6% and 10.8%, respectively, in which significant difference was found within the two groups (χ2=4.79, OR=1.88，95%CI: 1.06 - 3.33, P > 0.05). Conclusions G1704T polymorphism is associated with PDR presence and 1704G allele may increase the risk of PDR.
Inherited retinal degenerations (IRD) are a group of diseases with high genetic heterogeneity and differences in inheritance patterns, age of onset and severity of visual dysfunction. It is one of the leading causes of blindness. In recent years, gene therapy becomes a popular research area in the treatment of genetic diseases due to the rapid development of gene diagnosis technology. Several clinical trials worldwide have proved the safety and effectiveness of gene therapies in IRD. Clinical application of adeno-associated virus -mediated gene therapies for Leber congenital amaurosis and choroideremia clinical trials indicate that patients' retinal functions were improved at different levels after treatment. There are a number of other IRD clinical trials ongoing currently, which bring new possibilities to treat IRD. This article reviews the pathogenesis of IRD, gene vectors and clinical trials in IRD.
Objective To observe the relationship between endothelial constitutive nitric oxide synthase (ecNOS) genetic polymorphism and diabetic retinopathy（DR）of non insulindependent diabetes mellitus (NIDDM) patients of the Han nationality.Methods A total of 166 patients who clinical diagnosed with NIDDM as case group, 85 cases of patients (cataract or fracture) and healthy subjects without diabetes, hypertension and kidney disease,over 40 years old of age and without consanguinity between each other were selected as normal control group. Case group were divided into non-DR (NDR) group, nonproliferative-DR (BDR) group and proliferativeDR (PDR) group according to the result of fundus fluorescein angiography. Case group and normal control group subjects all were Han nationality. DNA was extracted from peripheral venous blood; the fourth 27 base pairs (bp) repeat polymorphism of ecNOS gene by was measured by polymerase chain reaction (PCR). Results The 27 bp repeat sequences within the ecNOS gene present in the Han nationality,allele b repeat 5 times, alleles a repeat 4 times. PCR results showed that there are 2 alleles and 3 genotypes in normal control, NDR, BDR and PDR group. The frequency of genotype bb、ab、aa were 80%, 16.5%, 3.5% in normal subjects; 77.2％, 13.9%, 8.9％ in NDR group; 80.5％, 17.1%,2.4％ in BDR group;78.3％, 13%, 8.7％ in PDR group,respectively. The allele frequency (chi;2 =1.841) and gene frequency (chi;2=3.847) were not statistically significant (P＞0.5) in normal control,NDR,BDR and PDR group. Logistic regression analysis showed that there is no relation between DR and ecNOS duplicated gene polymorphism. Conclusions There is 27 bp repeated polymorphism in 4th intron of ecNOS gene, which may not be associated with the DR of NIDDM in the Han nationality.
Olfactory bulb is a critical component in encoding and processing olfactory signals, characterized by its intricate neural projections and networks dedicated to this function. It has been found that descending neural projections from the olfactory cortex and other advanced brain regions can modulate the excitability of olfactory bulb output neurons in the olfactory bulb, either directly or indirectly, which can further influence olfactory discrimination, learning, and other abilities. In recent years, advancements in optogenetic technology have facilitated extensive application of neuron manipulation for studying neural circuits, thereby greatly accelerating research into olfactory mechanisms. This review summarizes the latest research progress on the regulatory effects of neural projections from the olfactory cortex, basal forebrain, raphe nucleus, and locus coeruleus on olfactory bulb function. Furthermore, the important role that photogenetic technology plays in olfactory mechanism research is evaluated. Finally, the existing problems and future development trends in current research are preliminarily proposed and explained. This review aims to provide new insights into the mechanisms underlying olfactory neural regulation as well as applications of optogenetic technology, which are crucial for advancing the research on olfactory mechanism and the application of optogenetic technology.
Objective To observe the opticin expression in the eyes of nonobese diabetes (NOD) mice and nondiabetic NOD mice.Methods Twenty NOD mice were divided into diabetic group (experimental group) and nondiabetic group (control group). All the mice were killed by cervical dislocation method.The eyes were harvested, and the vitreous, retina and sclera were separately collected. Western blot and realtime reverse transcriptionpolymerase chain reaction（RT-PCR）were respectively used to determine opticin protein and OPTC mRNA levels.Results The opticin protein level in the vitreous and retina was lower in the experimental group（t=4.42,4.58;P=0.002,0.002）,but is same in thesclera between the 2 groups（t=0.27,P=0.794）.OPTCmRNA level was vitreousgt;retinagt;sclera. OPTCmRNA levels of vitreous and retina in diabetic group were significantly lower（t=3.30,2.48；P=0.01,0.04）; there was no statistical significant on OPTC mRNA of sclera between two groups（t=0.27,P=0.80）.Conclusion Expression of opticin was suppressed in retina and vitreous of diabetic mice.