Microparticles are small vesicles that are released by budding of the plasma membrane during cellular activation and apoptotic cell breakdown. A spectrum of cell types can release microparticles including endothelial cells, platelets, macrophages, lymphocytes and tumor cells. Biological effects of microparticles mainly include procoagulant activity, inhibition of inflammation and cancer progression. The present study shows that vitreous microparticles isolated from proliferative diabetic retinopathy (PDR) stimulated endothelial cell proliferation and increased new vessel formation, promoting the pathological neovascularization in PDR patients. Oxidative stress induces the formation of retina pigment epithelium-derived microparticles carrying membrane complement regulatory proteins, which is associated with drusen formation and age related macular degeneration. Microparticles from lymphocyte (LMP) play an important role in anti-angiogenesis by altering the gene expression pattern of angiogenesis-related factors in macrophages. Besides, LMP are important proapoptotic regulators for retinoblastoma cells through reduction of spleen tyrosine kinase expression and upregulation of the p53-p21 pathway which ultimately activates caspase-3. However, how to apply the microparticles in the prevention and treatment of retinal diseases is a major challenge, because the study of the microparticles in the fundus diseases is still limited. Further studies conducted would certainly enhance the application of microparticles in the fundus diseases.
Open-globe injuries (OGI) result in complicated and diverse conditions with different mechanisms and anatomical locations, which lead to completely different outcomes based on when to perform pars plana vitrectomy (PPV) after trauma. The PPV operation time points are generally divided into early (0 - 3 days), delayed (4 - 14 days), and late (> 2 weeks). There are still some controversies about the PPV time points after OGI. Injuries with intraocular foreign bodies or high risk of infection usually need early surgery to reduce the occurrence of endophthalmitis. However corneal edema and vitreous hemorrhage can increase the difficulties for early diagnosis and surgery. If there is choroidal hemorrhage or severe trauma in the back part of the eye, delayed intervention can allow the blood clots to be liquefied and removed easily. But there is higher incidence of postoperative complications. Late surgery can reduce the difficulty of PPV, but the increased incidence of proliferative vitreoretinopathy may lead to severe retinal traction, tears and postoperative scar formation.
Proliferative vitreoretinopathy (PVR) is a common complication and major cause of blindness of ocular trauma. Many cytokines, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), participate in the process of the pathogenesis of traumatic PVR. VEGF competitively inhibits binding of PDGF to its receptor (PDGFRα), enables indirect activation of PDGFRα by non-PDGF ligands, resulting in reduced p53 expression, cell proliferation and migration, which is a key point in the pathogenesis of traumatic PVR.
Retinal microglial cells are immune cells of the retina and participate in the retinal immune response. In recent years, it has been found that microglia plays an important role in the pathogenesis of diabetic retinopathy (DR), and is involved in the pathological process of neurodegeneration and microvascular disease in DR. Understanding the function of retinal microglial cells and their role in the pathogenesis DR may open up new avenues for the treatment of DR through the precise regulation of microglia
Retinal ischemia-reperfusion injury (RIRI) is an important pathophysiological basis of diabetic retinopathy, glaucoma, central retinal arteriovenous obstruction and some other ischemic retinal diseases. At present, there are several theories about the pathogenesis of RIRI, which included oxidative stress, apoptosis, necrosis, necroptosis, vascular injury and inflammatory reaction. Aim at the above pathogenesis of RIRI, domestic and foreign scholars have put forward a lot of methods in treating RIRI, including anti-radical damage, anti-glutamic acid excitotoxicity, anti-apoptosis, anti-necrosis, anti-necroptosis, protection of tight junctions, protection of endothelial cells, anti-inflammatory response, etc. Although there are a lot of drug research on RIRI, the timing of drug interventions for RIRI is still unclear. It may achieve twice the result with half the effort to determine the most effective treatment time window, and will also play a vital guiding role in the clinical treatment of ophthalmic related diseases.
Epigenetics has become one of the major research directions of human genome after genome sequencing, and plays an important role in many complex pathophysiological processes such as tumor, biological development, aging and neuropathy. The metabolic memory phenomenon in diabetic retinopathy (DR) suggests that the pathogenesis of DR has a complicated relationship with epigenetic factors. Many studies show the changes and roles of histone modification, DNA methylation and non-coding RNA in the development of DR. However, the current understanding of how epigenetic modifications affect diseases is limited, and most studies on histone modifications have not been carried out in DR. There is still a lot of room for development in epigenetic research on DR. At the same time, epigenetic modification is very complicated, and how to integrate the interaction of different modifications in the development stage of DR is the focus of future research work.
Sympathetic ophthalmia (SO) is a bilateral granulomatous uveitis that occurs after single eye surgery or internal eye surgery. Its pathogenesis is not yet clear, and it is mostly considered to be an immune disease caused by exposure to autoantigens. The clinical diagnosis mainly depends on the patient's medical history, typical clinical manifestations and signs, and auxiliary ophthalmic imaging examinations such as FFA, ICGA, OCT. The clinical manifestations of SO are complex and variable, and the disease is prone to relapse, which may eventually lead to blindness. At present, treatment is mainly through systemic glucocorticoid therapy combined with immunosuppressive agents and/or biological agents. Understanding the typical imaging manifestations of SO is helpful to confirm the diagnosis early in the clinic, and timely provide reasonable drug treatment to improve the prognosis of patients.
The main treatment methods of macular edema (ME) are intravitreal injection of anti-vacular endothelial growth factor drugs, corticosteroids, retinal laser photocoagulation and pars plana vitrectomy (PPV). However, recurrent ME, epiretinal membrane formation and drug resistance have occurred to a part of patients, which is called refractory ME (RME). PPV with internal limiting membrane peeling (ILMP) has the potential of treating and relieving RME. PPV combined with ILMP can treat and relieve RME by removing the posterior vitreous cortex, or removing the epiretinal membrane or internal limiting membrane at the same time during surgery to relieve the traction between the vitreous body and the retina. However, due to the complex pathogenesis of ME, the therapeutic effects of PPV combined with ILMP on ME caused by different etiologies still need clinical studies to explore the best surgical methods for ME caused by different etiologies.
Rituximab (RTX) is a monoclonal antibody directed against the CD20 antigen expressed on B cells. It has been successfully employed in the treatment of non-Hodgkin's lymphoma and varied systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and granulomatosis with polyangiitis. Recently its efficacy in the treatment of ocular inflammatory diseases (OID), including refractory scleritis, peripheral ulcerative keratitis, uveitis, and ocular cicatricial pemphigoid, has aroused more concerns. The literature suggests that RTX may be useful for controlling the inflammation and decreasing or stopping the use of corticosteroids and other immunosuppressants in OID, which may contribute a new treatment alternative in patients with the recalcitrant and sight-threatening forms of OID. This article reviews the clinical application status of RTX in the treatment of OID.
ObjectiveTo observe the level of microparticles in the vitreous of patients with proliferative diabetic retinopathy (PDR), and preliminarily explore the role of microparticles in the pathogenesis of PDR.MethodsA case control study. From January to December 2018, 54 cases of 54 eyes of PDR patients (PDR group) and 20 cases of non-diabetic retinopathy patients (control group), who were diagnosed and treated with vitrectomy (PPV) in the Department of Ophthalmology, Tianjin Medical University General Hospital vitreous samples were included in the study. Among 54 eyes in the PDR group, there were 42, 21, and 17 eyes with vitreous hemorrhage (VH), traction retinal detachment (TRD), and previous intravitreal injection of drugs, respectively. Among the 20 eyes of the control group, idiopathic macular hole, idiopathic anterior macular membrane, vitreous macular traction syndrome, and complete lens dislocation were 6, 6, 2, and 6 eyes, respectively. The PDR group was divided into uncombined TRD group and combined TRD group according to PDR stage and whether TRD occurred, with 33 and 21 eyes, respectively. According to the presence or absence of VH, they were divided into groups with VH and without VH, with 42 eyes and 12 eyes, respectively. According to whether anti-vascular endothelial growth factor (VEGF) drugs were injected into the intravitreal cavity 3 days before PPV, they were divided into anti-VEGF drug group and no anti-VEGF drug group, with 17 eyes and 37 eyes respectively. The levels of retinal photoreceptor cells (RMP), platelets (PMP), endothelial cells (EMP) and phosphatidylserine (PS-MP) expressing on the membrane surface in the sample were detected by flow cytometry. The comparison between the two groups of samples was performed by t test, and the comparison between multiple groups of samples was performed by one-way analysis of variance or Mann-Whitney test.ResultsCompared with the control group, the vitreous RMP level of the PDR group was significantly decreased, and the EMP and PMP levels were significantly increased. The differences were statistically significant (t=−2.361, 5.064, 3.531; P=0.018, ＜0.001, 0.001). There was no statistically significant difference in PS-MP levels between the two groups (t=−1.617, P=0.110). Compared with the TRD group, the levels of RMP and PMP in the vitreous of the TRD group were significantly increased, and the difference was statistically significant (t=−2.221, −2.098; P=0.031, 0.041). The level of EMP in the vitreous body of the anti-VEGF drug group was significantly lower than that of the non-anti-VEGF drug group, however, it was still higher than the control group. The difference was statistically significant (Z=−2.430, −2.499; P=0.015, 0.012). The level of PMP in the vitreous body of the eye without VH was significantly higher than that in the group with VH, and the difference was statistically significant (t=−3.097, P=0.003).ConclusionsThe elevated levels of EMP and PMP in the vitreous of PDR patients may be related to the damage of retinal capillaries; intravitreal injection of anti-VEGF drugs before surgery can reduce the level of EMP. VH may be related to the procoagulant effect of PMP.