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.
To perform a meta-analysis of single nucleotide polymorphism needs to calculate gene frequency. This paper employs allele model as an example to introduce how to calculate gene frequency and display the process of a meta-analysis of single nucleotide polymorphism data using Review Manager 5.3 software.
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.
Retinal vein occlusion (RVO) is characterized by obstruction of retinal vein blood flow, distended flexion, retinal hemorrhage, edema, and neovascularization, and its pathogenesis is not completely clear. Recent studies have found that endothelin (ET)-1, ETA receptor and ETA signaling pathways in the ET system may be involved in the occurrence and development of RVO by stimulating vasoconstriction to increase retinal vein pressure and inducing the expression of pro-inflammatory factors such as TNF-α, IL-6 and IL-1β. In-depth understanding of the correlation between the ET system and the occurrence and development of RVO can provide new ideas for further research on the pathogenesis of RVO.
The suprachoroidal space is a potential space between the sclera and choroid. Suprachoroidal spacedrug delivery is becoming an applicable method to the ocular posterior segment diseases. Because it targets the choroid, retinal pigment epithelium and retina with high bioavailability and safety, while maintaining low levels elsewhere in the eye. In recent years, new discoveries has been carried out in different areas of interest, such as drug delivery methods, pharmacokinetics and clinical trials. Clinical trials with suprachoroidal space injection of triamcinolone acetonide are executed with promising findings for patients with noninfectious uveitis and diabetic macular edema. Suprachoroidal space triamcinolone acetonide injectable suspension is the first and currently the only agent specifically approved for uveitic macular edema by Food and Drug Administration. Nowadays, many clinical trails with suprachoroidal space drug delivery have been explored, although there are still many risks and uncertainties. With the development of technology in the future, suprachoroidal space drug delivery appears to be a promising treatment modality for ocular posterior segment diseases.
The hallmark lesions of age-related macular degeneration (AMD) are drusen and basal linear deposit which are lipid substances deposited in Bruch membrane or the compartment on the Bruch membrane. There is a prevailing hypothesis that lipid and its oxidized derivant deposited in retina may have important roles in the pathogenesis of AMD. Lipid oxidation products are toxic, may affect the adjacent cells, induce inflammation, and trigger neovascularization.7-ketocholestoral (7KCh), a naturally occurring oxidized form of cholesterol, had been found to be toxic to retinal cells and able to induce chronic inflammation, which may play a critical role in the development of AMD. However the precise mechanism remains to be elucidated. Thus we will make a brief review of 7KCh and its association with AMD.
【Abstract】Objective To compare radiologists’ performance on combined unenhanced and feridexs-enhanced MR imaging (MRI) with their performance on helical CT enhanced, unenhanced MRI, and feridexs-enhanced MR alone imaging for the characteristics of local hepatic lesions. Methods MR images and CT scans obtained in 26 patients with 57 local hepatic lesions were analyzed with reviewer operator characteristic (ROC) curve analysis. The imaging of patient were divided into 4 groups including combined unenhanced and feridexs-enhanced MRI group, helical CT enhanced group, unenhanced MRI group, and feridexsenhanced MR alone group. Results The combined approach resulted in larger area under the ROC curve (Az=0.926 0) and accuracy (86.8%),P<0.05,as compared with the others methods. There were no significant differences among the other three methods. Conclusion Feridexs-enhanced MRI was more accurate than enhanced helical CT scan in characterization of local hepatic lesion. The combined analysis of unenhanced and feridexs-enhanced images was more accurate in the characterization of focal hepatic lesions than was review of feridexs-enhanced images alone.
The incidence of myopia is increasing year by year and the trend of younger age is obvious. The situation of myopia prevention and control is very serious. The sclera is the target organ for the development of myopia. When myopia occurs and develops, the ultrastructure of the sclera tissue will undergo pathological changes, resulting in a decrease in its tensile strength, then progressive axial growth and posterior sclera expansion. Scleral collagen cross-linking can effectively increase the hardness and tensile strength of scleral tissue, which may have great potential in the prevention and control of myopia, especially pathological myopia. At present, the effectiveness of scleral collagen cross-linking technology in the prevention and treatment of pathological myopia researches are still in the stage of animal experiments, and there are a lot of controversies on the safety. The development of any new technology to ensure safety is the primary condition. A comprehensive understanding of the safety of scleral collagen crosslinking in the prevention and control of myopia can provide more basis and guidance for the further study of scleral collagen crosslinking.
Vascular endothelial growth factor (VEGF) is a multifunctional factor that promotes blood vessel formation and increases vascular permeability. Its abnormal elevation plays a key role in common retinal diseases such as wet age-related macular degeneration and diabetic macular edema. Anti-VEGF therapy can inhibit angiogenesis, reduce vascular leakage and edema, thereby delaying disease progression and stabilizing or improving vision. Currently, the clinical application of anti-VEGF drugs has achieved satisfactory therapeutic effects, but there are also issues such as high injection frequency, heavy economy burden, potential systemic side effects, and non-responsiveness. To address these issues, current research and development mainly aim on biosimilars, multi-target drugs, drug delivery systems, oral anti-VEGF drugs, and gene therapy. Some drugs have shown great potential and are expected to turn over a new leaf for anti-VEGF treatment in ophthalmology.
Uric acid (UA) is the final product of human purine metabolism. As one of the main antioxidants in the body, it can scavenge oxidative radicals. Under the action of oxidative-antioxidant shuttle mechanism, the antioxidant activity of UA can be reversed, causing inflammation and oxidative stress of vascular endothelial cells. Hyperuricemia (HUA) is considered to be one of the major risk factors for diabetes and diabetic nephropathy. The study of HUA in diabetic retinopathy (DR) is also a hot topic. UA can cause retinal vascular sclerosis, and affect the occurrence and development of DR by promoting oxidative stress and inducing neovascularization.