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.
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.