Based on the pathogenic mechanisms of age-related macular degeneration (AMD), tremendous preclinical and clinical trials have demonstrated that cell transplantation which aim to replace impaired retinal pigment epithelium (RPE) with healthy RPE cells is a promising approach to treat AMD. So far, choices of cell sources mainly are autologous RPE, iris pigment epithelium, fetal RPE, human embryonic stem cell-derived RPE and human induced pluripotent stem cell-derived RPE, and some of them are undergoing clinical researches. Grafting manners in cell-based therapies are various including RPE sheet or RPE-choroid complex transplantation, RPE cell suspension injection, and RPE sheet transplantation with scaffolds. This review is limited to cell-based therapies for RPE that damaged first in the progress of AMD and focus on recent advances in cell sources, transplantation methods, preclinical and clinical trials, and the obstacles that must be overcome.
Clustered regularly interspersed short palindromic repeats/Cas system is a powerful genome-editing tool for efficient and precise genome engineering both in vitro and in vivo, with the advantages of easy, convenient and low cost. This technology makes it possible to simultaneously mutate multiple genes in a single fertilized egg, thus to study the gene expression, genetic interaction and gene function. Even though this method is still in its immature stage and its stability is inconclusive, making precision models of ocular diseases through genome editing may provide a positive effect to explore gene targeted therapy in genetic eye disease.
Replacement of diseased retinal pigment epithelium (RPE) cells with healthy RPE cells by transplantation is one option to treat several retinal degenerative diseases including age-related macular degeneration, which are caused by RPE loss and dysfunction. A cellular scaffold as a carrier for transplanted cells, may hold immense promise for facilitating cell migration and promoting the integration of RPE cells into the host environment. Scaffolds can be prepared from a variety of natural and synthetic materials. Strategies, such as surface modification and structure adjustment, can improve the biomimetic properties of the scaffolds, optimize cell attachment and cellular function following transplantation and lay a foundation of clinical application in the future.
Single cell RNA sequencing technique provides a strong technical support for the analysis of cell heterogeneity in biological tissues, and has been widely used in biomedical research. In recent years, considerable scRNA-seq data have been accumulated in the research of ocular fundus diseases. The ocular fundus is abundant for the network of vessel and neuron, which leads to the complicated pathogenesis of fundus diseases. Through single cell RNA sequencing technique, the expression of thousands of genes of certain cell types or even subtypes can be obtained in the disease environment. Single cell RNA sequencing technique accurately reveals the pathogenic cell types and pathogenic mechanisms of ocular fundus diseases such as neovascular retinopathy, which provides a theoretical basis for the birth of new diagnosis and treatment targets. The construction of multi-omics single-cell database of ocular fundus diseases will enable high-quality data to be further explored and provide an analysis platform for ophthalmic researchers.
Lactate was originally thought to be a metabolic waste product of glycolysis produced by cells in hypoxic environment. In recent years, increasing evidence has indicated that lactate plays a crucial role in the physiological and pathological processes of the retina. Lactate is transported via monocarboxylate transporters in different retinal cell types such as photoreceptor cells and Müller cells to maintain the high metabolic demand of the retina. In addition to serving as oxiditive substrate for energy, lactate can mediate intracellular signal transduction through receptor G protein-coupled receptor 81, participating in the maintenance of retinal homeostasis and the progression of pathological neovascularization. Moreover, lactate-mediated protein lactylation directly regulates gene expression in microglia and T lymphocytes, which has gradually become a new hotspot in the field of retinal pathological neovascularization and neuroinflammation. Therefore, the regulation of lactate metabolism may provide novel perspectives for the treatment of retinal lactic acid metabolism disorders such as age-related macular degeneration and retinitis pigmentosa.
ObjectiveTo apply the multi-modal deep learning model to automatically classify the ultra-widefield fluorescein angiography (UWFA) images of diabetic retinopathy (DR). MethodsA retrospective study. From 2015 to 2020, 798 images of 297 DR patients with 399 eyes who were admitted to Eye Center of Renmin Hospital of Wuhan University and were examined by UWFA were used as the training set and test set of the model. Among them, 119, 171, and 109 eyes had no retinopathy, non-proliferative DR (NPDR), and proliferative DR (PDR), respectively. Localization and assessment of fluorescein leakage and non-perfusion regions in early and late orthotopic images of UWFA in DR-affected eyes by jointly optimizing CycleGAN and a convolutional neural network (CNN) classifier, an image-level supervised deep learning model. The abnormal images with lesions were converted into normal images with lesions removed using the improved CycleGAN, and the difference images containing the lesion areas were obtained; the difference images were classified by the CNN classifier to obtain the prediction results. A five-fold cross-test was used to evaluate the classification accuracy of the model. Quantitative analysis of the marker area displayed by the differential images was performed to observe the correlation between the ischemia index and leakage index and the severity of DR. ResultsThe generated fake normal image basically removed all the lesion areas while retaining the normal vascular structure; the difference images intuitively revealed the distribution of biomarkers; the heat icon showed the leakage area, and the location was basically the same as the lesion area in the original image. The results of the five-fold cross-check showed that the average classification accuracy of the model was 0.983. Further quantitative analysis of the marker area showed that the ischemia index and leakage index were significantly positively correlated with the severity of DR (β=6.088, 10.850; P＜0.001). ConclusionThe constructed multimodal joint optimization model can accurately classify NPDR and PDR and precisely locate potential biomarkers.