Mesenchymal stem cells (MSCs) are considered as an ideal treatment for multiple diseases including ocular disease. Recent studies have demonstrated that MSCs-derived exosomes have similar functions with MSCs. Exosomes are nanovesicles surrounded by a phospholipid layer that shuttle active cargo between different cells. They are capable of passing the biological barrier and have potentials to be utilized as natural carrier for the ocular drug delivery.
Glucocorticoids (GCS) are the main treatment for non-infectious uveitis (NIU). However, long-term GCS treatment may induce systemic side effects including hypertension, hyperlipidemia and diabetes. Patients may develop cataract, ocular hypertension or glaucoma because of topical application of GCS. Rapamycin (RAPA) exhibits immunosuppressive, antiangiogenic and antiproliferative effects. Animal experiments and clinical trials have shown that RAPA has therapeutic potential for NIU, especially the treatment of intravitreal injection. In particular, intravitreal injection of RAPA can result in minimal systemic exposure and reduce adverse events. Meanwhile, systemic unwanted effects should be concerned about. In recent years, some studies have attempted to employ nanostructured carriers to improve penetrating abilities of RAPA and efficacy of treatment for ocular posterior segment diseases. These carriers include micelles, liposomes, nanocrystals, polymeric nanoparticles, magnetic nanoparticles and so on. Whether they can load RAPA for treating NIU deserves further study and exploration.
Behcet's Disease (BD) is a multisystem vasculitis characterized by disease alternated with recurrent episodes and remissions, involving genital, oral, ocular uvea, cutaneous, and articular manifestations. The nuclear factor (NF)-κB signaling pathway paly an important role in the BD progression. It encompasses diverse gene, protein, and cellular regulatory mechanisms operating across various levels, alongside microbiological and experimental studies involving animals and cells. At the protein research findings, activation of the NF-κB pathway in BD patients is marked by elevated plasma levels of soluble CD40 ligand, which stimulates neutrophils to release reactive oxygen species and extracellular traps, thereby promoting inflammation. At the cellular research findings, macrophages in BD patients polarize towards classically activated macrophages phenotype through the NF-κB pathway, exacerbating the inflammatory response. The activation of NF-κB is associated with increased expression of anti-apoptotic proteins in T cells, leading to prolonged inflammation. Microbiological investigations reveal that the decreased gut microbiota diversity in BD patients compromises intestinal barrier integrity. NF-κB pathway involvement in regulating neutrophil and type 1 helper T cell (Th) 1/Th17 cell function worsens inflammation. Genetically, BD patients exhibit polymorphisms in immune regulatory genes, which contribute to inflammation through the NF-κB pathway. Mutations in NF-κB-associated genes elevate the risk of BD, while mutations in the endogenous inhibitor A20 lead to abnormal NF-κB activity, sustaining inflammation. Animal experiments and in vitro experiments corroborate the efficacy of NF-κB inhibitors in attenuating inflammation. Targeting upstream inflammatory factors within the NF-κB pathway yields positive outcomes in BD patients. In summary, the NF-κB signaling pathway plays a pivotal role in the development of BD. Developing NF-κB inhibitors may open new avenues for treating BD. Further research is necessary to comprehensively elucidate the precise mechanisms by which NF-κB operates in the pathogenesis of BD, as well as its potential clinical applications in therapy.
Monocyte chemoattractant protein-1(MCP-1) is a cytokine which belongs to the CC chemokine family. Retinal pigment epithelium (RPE) cells, photoreceptors and microglial cells in the retina can secrete MCP-1. Physiological level of MCP-1 is important for preserving morphology of RPE and glial cells, as well as retinal function and gross morphology. MCP-1 is likely released from Müller glia and the RPE cells when retina under stress, and attracts microglia/macrophages to the sites of retinal damage, activates the microglia to ingest cell debris. MCP-1 has been found upregulated in the intraocular fluid of retina in patients and animal models with retinal detachment, posterior uveitis and age-related macular degeneration. The expression of MCP-1 may be response to retinal inflammation. Therefore, it is tempting to speculate that pharmacological targeting of MCP-1 may be a safe and viable strategy in treatment of retinal disease.
Objective To evaluate the effect of 27G pars plana vitrectomy (PPV) and 25G PPV on idiopathic epiretinal membrane (IMEM). Methods Thirty-eight eyes of 38 patients with IMEM were enrolled into this retrospective and comparative study. Eighteen eyes were treated with 27G PPV (group A), 20 eyes underwent 25G PPV (group B) voluntarily. The best corrected visual acuity (BCVA), intraocular pressure (IOP), slit-lamp microscope, indirect ophthalmoscopy, fundus color photograph, ocular coherence tomography (OCT) and counting of corneal endothelial cells (CEC) were examined before the surgery. BCVA results were converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity. There was no statistically significant difference between two groups in terms of BCVA, IOP, foveal macular thickness (FMT), the counting of CEC and CEC hexagon rate before the surgery (t=1.627, 0.860, 0.293, 1.238, 0.697;P＞0.05). All operations were performed by the same doctor. Operation time for vitrectomy and peeling membrane was recorded. BCVA, IOP, OCT, FMT, counting of CEC and the improvement of metamorphopsia were observed on 1, 7 days and 1, 3 months after PPV. Results The mean operation time for vitrectomy in group A and B were (6.7±2.8), (10.5±3.3) min, respectively. The mean operation time for vitrectomy in group A was significantly longer than that in group B (t=3.084,P＜0.05). The mean operation time for peeling membrane in group A and B were (10.2±5.2), (11.0±5.9) min, respectively. There was no statistically significant difference between two groups in terms of the time for peeling membrane (t=1.970,P=0.187). On 1, 7 days and 1, 3 months after PPV, the difference of BCVA (t=1.463, 0.683, 0.961, 1.226;P=0.833, 0.509, 0.699, 0.744) and IOP (t=1.314, 1.262, 0.699, 1.116;P=0.763, 0.721, 0.534, 0.712) between two groups were not statistically significant. On 1 day after PPV, there were 2 eyes and 5 eyes with ＜9 mmHg (1 mmHg=0.133 kPa) IOP in group A and B. On 7 days and 1, 3 months after PPV, the difference of FMT between two groups were not statistically significant (t=1.257, 1.368, 1.437;P=0.735, 0.745, 0.869). On 3 months after PPV, the difference of CEC between two groups were statistically significant (t=2.276,P＜0.05); the difference of hexagon rate between two groups were not statistically significant (t=1.473,P=0.889). Conclusion The efficacy of 27G PPV for IMEM appears similar to 25G PPV. But 27G PPV has a shorter operating time for vitrectomy, a more stable IOP and a minimal damage to CEC.
Acquired syphilis uveitis, due to lack of the characteristic features, presents with various types. The most common type is posterior uveitis and panuveitis, including chorioretinitis, retinal vasculitis, optic nerve retinitis. The diagnosis and assessment of response to treatment depends mainly on the serological diagnostic tests, including nontreponemal and treponemal test. Acquired syphilis uveitis often presents with manifestations similar to various types of uveitis, especially to autoimmune uveitis and other infectious uveitis, so differential diagnosis is important. The gold standard treatment for active syphilitic uveitis is penicillin G, or doxycycline if patient is allergy to penicillin. Clinically misdiagnosis and delayed treatment may result in irreversible visual impairment and severe systemic and eye complications. However such timely treatment always has a good prognosis.
The pathogenesis of diabetic retinopathy (DR) is complicated and has not yet been fully elucidated. To explore the pathogenesis of DR and the mechanism of drug action, proteomics through quantitative analysis techniques is very useful. It can analyzes differentially expressed proteins in the retina, vitreous fluid, aqueous humor, tears, and blood of DR patients and diabetic rats, and analyzes differentially expressed proteins after drug intervention. This paper is a review of the progress in proteomic research of DR in recent years.
Primary vitreoretinal lymphoma (PVRL) is one of the most common type of primary intraocular lymphoma. The current treatment options include local ocular radiotherapy (radiotherapy), systemic chemotherapy (chemotherapy), local ocular chemotherapy, and combination therapy. The treatment options are different at different stages of PVRL, however, there is no uniform treatment guideline. Local ocular chemotherapy can make the drug reach effective therapeutic concentration in the eye, and it can be repeated many times. At the same time, it can avoid the adverse reactions caused by systemic medication or radiotherapy. It is an ideal choice for relieving ocular symptoms. At present, the mainstream ocular local chemotherapeutics are methotrexate (MTX) and rituximab (RTX). The basic consensus about the intravitreal injection of MTX (IVM) is the induction-consolidation-maintenance model, however, the time of each stage and frequency of IVM are diverse. The time interval of intravitreal injection of RTX is also variable, ranging from 1 time/week to 1 time/months and so on. Corneal epithelial lesions caused by frequent MTX injections and the higher recurrence rate after RTX treatment are the main reasons for changing the treatment plan. For patients with primary central nervous system lymphoma and PVRL, combined treatment with neurology department is necessary to save patient's lives, ophthalmology treatment relieves ocular symptoms and improves the patient's quality of life. For patients with PVRL alone without central nervous system involvement, ophthalmology treatment is necessary to control patient's eye symptoms, and close follow-up should be followed to find the involvement of the central nervous system in time, and then combined with neurological treatment to save patient’s lives.
As a new treatment option after conventional corticosteroids and immunomodulatory drugs, biologics have been widely used in the clinical management of non-infectious uveitis in many countries due to their approved efficacy and safety. Anti-tumor necrosis factor-alpha monoclonal antibody is the most commonly used one. However, the guidance on its standardized application is lacking. The Ocular Immunology Group of Immunology and Rheumatology Academy in Cross-Straits Medicine Exchange Association compiled the Chinese expert consensus on treatment of non-infectious uveitis with anti-tumor necrosis factor-alpha monoclonal antibody. This evidence-based consensus is made according to the principle of consensus building and combines the clinical experience of the experts. Twelve recommendations are formatted on the application of Adalimumab and Infliximab. The interpretation of this consensus point will help improve the normative and effective application of anti-tumor necrosis factor-alpha monoclonal antibody in ophthalmologists, rheumatologists and immunologists.
ObjectiveTo investigate the effect of repairing radial bone defect with scaffold material of attapulgite/collagen type I/poly (caprolactone) (ATP/Col I/PCL) in rabbits and the possibility as bone graft substitutes. MethodsATP/Col I/PCL materials were prepared via adding ATP to hexafluoroisopropanol after dissolved Col I/PCL (3∶2), and Col I/PCL materials via dissolving Col I/PCL (3∶2) in hexafluoroisopropanol served as control. The structure of scaffolds was observed under scanning electron microscope (SEM). Twenty-four Japanese white rabbits (male, 2 months old) were used to establish the bilateral radius defect model of 15 mm in length, and randomly divided into group A (6 rabbits, 12 defects), group B (9 rabbits, 18 defects), and group C (9 rabbits, 18 defects); then the Col I/PCL scaffold was implanted in the bone defect area in group B, the ATP/Col I/PCL scaffold in group C, no treatment was done in group A as control. The general condition of rabbits was observed after operation, and bone defect repair was evaluated by X-ray at 4, 8, and 12 weeks. At 12 weeks, the tissue of defect area was harvested for the general, SEM, Micro-CT, histological, and immunohistochemical staining to observe defect repair and material degradation. ResultsSEM observation showed that two kinds of materials were porous structure, ATP/Col I/PCL structure was more dense than Col I/PCL. All animals survived to the end of experiment, and no incision infection occurred during repair process.X-ray films showed that the bone marrow cavity was re-opened in defect area of group C with time, the repair effect was superior to that of groups A and B. At 12 weeks after operation, general observation showed that scaffold material had good fusion with the surrounding tissue in groups B and C, defect was filled with connective tissue in group A. SEM indicated that the surface and pore of the scaffold were covered with a large number of cells and tissues in groups B and C. Micro-CT demonstrated that the new bone volume, bone mineral content, tissue mineral content, and connectivity density of group C were significantly higher than those of groups A and B (P<0.05). The observation of histology and immunohistochemical staining indicated that there were lots of connective tissues in defect area of group A, and ALP, Col I, and OPN were weakly expressed; there were many collagen fibers in scaffold degradation area in group B, and the expression levels of ALP, Col I, and OPN were higher than those of group A; there was few new bone in group C, the degradation rate of the scaffold was slower than that of group B, and the expression of Col I and OPN were enhanced, while ALP was weakened when compared with groups A and B. ConclusionATP/Col I/PCL composite scaffold material can degrade in vivo, and has dense three-dimensional porous structure, good biocompatibility, and high potentiality of bone repair, so it can be used as bone substitute material.