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
ObjectiveTo observe the expression of vascular endothelial growth inhibitor (VEGI, TL1A), vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in diabetes rats' serum, vitreous and retina, and discuss the role of VEGI in the pathogenesis of diabetic retinopathy (DR). MethodsA total of p70 adult male Wistar rats were randomly divided into 4 groups, the control group (10 rats), the diabetes mellitus (DM) 1 month group (20 rats), the DM 3 month group (20 rats) and the DM 6 month group (20 rats). Cytokines of serum and vitreous were determined by enzyme-linked immunosorbent assay (ELISA), and the concentrations of the cytokines in the retina were determined by immunohistochemistry on paraffin retinal sections. Hematoxylin-eosin (HE) staining of retina was used to estimate the pathological change of DR. The results were analyzed by one-way analysis of variances, independent samples t-test and LSD test. ResultsThe serum TL1A levels of the control group, the DM 1 month group, the DM 3 month group and the DM 6 month group rats were (92.09±2.05), (118.36±8.30), (85.90±7.51) and (78.90±4.88) ng/L respectively, the level of TL1A in serum of the DM 1 month group, the DM 3 month group and the DM 6 month group were significantly lower than that of the control group (F=77.405, P < 0.05). The concentration of serum TNF-α and IL-1β increased after DM model was established (F=3.508, 15.416; P < 0.05); the VEGF level in serum showed no difference between the groups (F=1.242, P > 0.05). The vitreous TL1A levels of the control group, the DM 1 month group, the DM 3 month group and the DM 6 month group were (91.50±8.18), (67.03±6.74), (47.44±4.92) and (46.01±4.62) ng/L respectively, every DM groups showed significant difference with the control group (F=114.777, P < 0.05); VEGF level in vitreous increased from 1 month after DM model was established (F=8.816, P < 0.05); TNF-α and IL-1β level in vitreous also showed an upward tendency (F=4.392, 3.635; P < 0.05). Paraffin section immunohistochemistry showed that the absorbance (also called optical density) of TL1A of the DM 1 month group and the DM 3 month group were significantly lower than that of the control group (t=6.851, 6.066; P < 0.05), but the DM 6 month group showed no difference with the control group (t=1.401, P > 0.05); the level of VEGF and TNF-α in DM groups were higher than that of the control group (tVEGF=-4.709, -16.406, -9.228; tTNF-α=-4.703, -6.583, -17.762; P < 0.05); the level of IL-1β were significantly higher in the DM 1 month group and the DM 6 month group (t=-4.108, -3.495; P > 0.05); but the DM 3 month showed no difference with the control group (t=-0.997, P > 0.05). HE staining of retina showed that the retina of the control group and the DM 1 month group had normal retinal structures, the DM 3 month group had retinal edema and disorganization, the DM 6 month group had severe retinal edema, deep stain of ganglion cells, and more neovascularization in inner plexiform layer. ConclusionVEGI is involved in the pathogenesis of DR, and it might interacts with VEGF, TNF-α and IL-1β to affect the development of DR.
ObjectiveTo observe the effect and complications of vitrectomy combined with intraocular silicon oil or C3F8 filling for proliferative diabetic retinopathy (PDR). MethodsEighty-six consecutive patients (101 eyes) with PDR-related vitreous hemorrhage who underwent primary standard three-port vitrectomy and intraocular tamponade of silicone oil or C3F8 were included in this retrospective study. They were divided into silicone oil group and C3F8 groups. There was no statistically significant difference between these two groups of patients for gender, age, duration of diabetes, fasting glucose, history of hypertension, diabetic kidney disease history, history of cardiac and vascular diseases, body mass index and smoking history. There was statistically significant difference between these two groups of patients for visual acuity (Z=-2.604, P=0.009). There was no statistically significant difference between these two groups of patients for intraocular pressure before surgery (Z=0.064, P=0.949). The mean follow-up was (20.3±16.4) months with a range from 1 to 47 months. The patients were followed up for visual acuity, intraocular pressure, neovascular glaucoma (NVG), the incidence of retinal detachment, recurrent vitreous hemorrhage, and repeated operation for complications. ResultsVisual acuity (t=-3.932, -8.326; P=0.000, 0.000) and intraocular pressure (t=-3.159, -2.703; P=0.006, 0.009) were changed significantly after surgery for both groups. Between these two groups after surgery, there were significant differences of visual acuity (Z=-1.879, P=0.040), intraocular pressure (Z=-3.593, P=0.000), and complications (revision operation, retinal detachment, recurrent vitreous hemorrhage and NVG) (t=-2.777, -2.102, -2.308, -2.013; P < 0.05). ConclusionIntraocular silicone oil tamponade can reduce the postoperative complications of PDR, especially for severe retinal neovascularization, exudation associated with retinal edema.
Pyroptosis is an inflammatory form of programmed cell death, including canonical and non-canonical pyroptosis pathway. Studies on pyroptosis have been reported in a variety of retinal diseases, but they are more focused on common diseases such as diabetic retinopathy and age-related macular degeneration. Many retinal diseases are difficult to treat because of the complexity of their etiology and pathogenesis. The discovery of pyroptosis has brought new content to the pathogenesis of these diseases, and also pointed a new direction for the treatment. Pyroptosis does not occur independently, and it is related to apoptosis and autophagy, but the specific mechanism is not clear. However, the most important biomolecule in the process of pyroptosis have been basically determined, and some methods can be used to interfere with pyroptosis, which has obtained preliminary achievement, suggesting that inhibition of pyroptosis may be a new direction for the treatment of retinal diseases and has broad research prospects.
ObjectiveTo observe the effect of interleukin (IL) 10 modified endothelial progenitor cells (EPC) in diabetic retinopathy (DR). MethodsEPC cells were collected and cultivated from the bone marrow of rats and identified by immuno-fluorescence staining. EPC cells were infected with lentivirus (LV) of EPC-LV-IL10-GFP (EPC-LV-IL10-GFP group) or EPC-LV-NC-GFP (GFP group). EPC cells without lentivirus infection was the EPC group. Enzyme-linked immuno sorbent assay (ELISA) was used to measure the concentrations of tumor necrosis factor (TNF)-α, IL10, IL8 and vascular endothelial growth factor (VEGF) in the supernatant of these three groups. 168 male Wistar rats were divided into normal control group (28 rats), diabetes mellitus (DM) group (28 rats), DM-blank control group (56 rats) and DM-intervention group (56 rats). DM was introduced in the latter 3 groups by streptozotocin intravenous injection. Three months later, the rats in the DM-blank control group and DM-intervention group were injected with EPC-LV-NC-GFP or EPC-LV-IL10-GFP by tail vein, respectively. Immunohistochemistry was used to observe the GFP expression in rat retinas. The blood-retinal barrier breakdown was detected by Evans blue (EB) dye. The retinal histopathologic changes were observed by transmission electron microscope. The mRNA level of VEGF, matrix metallproteinases-9 (MMP-9), angiopoietin-1 (Ang-1), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in retina were measured by reverse transcription-polymerase chain reaction (RT-PCR). ResultsELISA showed that the levels of TNF-αand IL8 in the supernatant significantly decreased, while the levels of IL10 and VEGF increased (P < 0.05) in EPC-LV-IL10-GFP group. GFP expressed in the retina of blank control group and intervention group, mainly in the ganglion cell layer, inner nuclear layer and outer plexiform layer. The retinal blood vessel pathological change and EB permeability significantly decreased in intervention group compared with DM group (P < 0.05), and blank control group (P < 0.05). RT-PCR revealed that the mRNA level of VEGF, MMP-9 and Ang-1 significantly increased, and eNOS decreased in DM group compared to the normal control group (P < 0.05). The mRNA level of VEGF and iNOS decreased, eNOS increased while Ang-1 and MMP-9 had not changed in DM-blank control group and DM-intervention group compared with DM group (P < 0.05). ConclusionsIL10 modified EPC can improve the inflammative microenvironment and suppressed the pathogenesis of DR. Furthermore, EPC transplantation can increase the number of EPC and exerted their effect.
Objective To observe the clinical features and prognosis of endogenous bacterial endophthalmitis (EBE). Methods Ten eyes of 10 patients diagnosed with unilateral EBE were retrospectively reviewed, including 7 males and 3 females. The mean age was 57.6±10.8 years old. Eight patients were with diabetes and 7 of them were diagnosed over 5 years. There were 3 patients with hepatocirrhosis, 1 patient with hypertension, and 1 patient with coronary disease. Nine cases had infectious diseases, including liver abscess (7 cases), pulmonary infection (3 cases), erysipelas (1 case) and perianal abscess (1 case). Seven cases had fever history. Culture and drug sensitive tests for aerobic bacteria, anaerobic bacteria and fungal were performed for 9 eyes using vitreous samples from the procedures of vitrectomy and/or intravitreal injection. All patients were treated with broad-spectrum antibiotics and adjusted for drug use according to microbiological culture and drug sensitivity test results. After the diagnosis was established, vitrectomy combined with lens removal was performed in 5 hours (3 eyes) and 24 hours (5 eyes); Vitreous tamponade of C3F8 (1 eye) and silicone oil (7 eyes) was used; At the end of the operation, 0.1 ml vancomycin (1 mg) and 0.1 ml ceftazidime (1 mg) were injected into the vitreous cavity. One eye received intravitreal injection of 0.1 ml vancomycin (1 mg) and 0.1 ml ceftazidime (mg), one eye received evisceration. During the follow up period from 6 to 24 months, visual function, slit lamp and fundus examinations were performed at each office visit. Results All patients complained of blurred vision and 5 patients had ocular pain. The visual acuity was no light perception (3 eyes), light perception (5 eyes); hand motion (1 eye) and 0.1 (1 eye). Corneal edema was found in all 10 eyes; hypopyon in 8 eyes; diffuse vitreous opacity in 10 eyes, including 3 eyes with retinal detachment. For 8 eyes treated by vitrectomy and intravitreal injection, 1 eye was eviscerated due to uncontrolled inflammation. The eye treated with intravitreal injection was enucleated for its uncontrolled inflammation. For 9 eyes received vitreous culture and drug testing, 8 eyes (88.9％) had positive results, including 5 eyes with Klebsiellar pneumonia, and 1 eye with Staphylococcus aureus, or Streptococcus agalactiae or Enterococcus faecalis respectively. At last office visit, 2 eyes were with no light perception; 4 eyes were with hand motion; and 1 eye with visual acuity of 0.1. Conclusions Most of the patients with endogenous bacterial endophthalmitis have systemic predisposing factors. Klebsiella pneumoniae is the leading cause of ocular EBE. Vitrectomy combined with intravitreal injection of antibiotics showed efficacy in treating EBE.