Activation Of Macrophage-like Cells Research Articles

Longitudinal Observation of Retinal Response to Optic Nerve Transection in Rats Using Visible Light Optical Coherence Tomography.

To characterize rat retinal responses after optic nerve transection (ONT) by visible-light optical coherence tomography (vis-OCT). Unilateral ONT was performed in Brown Norway rats (n = 8). In vivo, vis-OCT retinal imaging was performed on the experimental eyes before ONT (baseline), and two days, one week, two weeks, and four weeks (endpoint) after ONT, as well as on fellow eyes at the endpoint. The system was operated at a 70 kHz A-line sampling rate with both raster scans (512 × 2 × 512 A-lines), and circular scans (2048 × 100 A-lines) acquired around the optic disc. Retinal layers were segmented to calculate layer thicknesses and project en face images for visualization and quantifications. Vessel densities and oxygen saturation were used to evaluate the morphologic and functional impact on the retinal vasculature. After ONT, retinal nerve fiber bundles demonstrated significant degeneration, starting at two weeks, with a reduction of thicknesses quantified on the nerve fiber layer, ganglion cell complex, and total retina. Along with that, the activation of macrophage-like cells in the vitreoretinal interface was also observed. Vessel densities for all three retinal plexuses were unaffected over the period of observation. However, oxygen saturation in retinal arteries and veins was significantly reduced at four weeks after ONT. Vis-OCT can provide high-definition, in vivo characterization of retinal responses to ONT in rats. Despite a significant reduction in retinal layer thickness, this was not accompanied by alterations in vascular density. Despite this, oximetry indicates reduced retinal oxygen saturation, suggesting that altered vascular physiology is not reflected in the anatomic appearance of retinal blood vessel density alone.

Increased Macrophage-like Cell Density in Retinal Vein Occlusion as Characterized by en Face Optical Coherence Tomography.

Objectives: to quantitatively analyze macrophage-like cells (MLCs) at the vitreoretinal interface in retinal vein occlusion (RVO) using swept-source optical coherence tomography angiography (SS-OCTA) and en face optical coherence tomography (OCT). Methods: The study included 72 RVO patients, with 43 acute patients and 29 chronic patients. For a normal control, 64 fellow eyes were included. MLCs were visualized in a 5 μm en face OCT slab above the vitreoretinal interface centered on the fovea. After semi-automatic binarization and quantification, we evaluated the MLC count and density among groups. We also investigated the MLC density and distribution relative to retinal edema. Results: Morphological changes and congregation of MLCs appeared in RVO eyes. The MLC density of both the acute and chronic groups was significantly higher than that of the control eyes (p < 0.001). In the acute group, the MLC density of the edematous region was lower than both the non-edematous region (p < 0.001) and the whole image (p < 0.01). The MLC density in acute eyes was negatively correlated to central fovea thickness (CFT) (r = −0.352, p < 0.05). The MLC density in chronic eyes was positively correlated to CFT and mean retina thickness (MRT) (r = 0.406, p < 0.05; r = 0.412, p < 0.05, respectively). Conclusions: SS-OCTA is a viable and simple method for the characterization of MLCs at the vitreoretinal interface. A significant increase in the MLC density in both acute and chronic eyes implicates the activation and recruitment of MLCs in RVO and that the MLC density and distribution can be affected by retinal edema.

Inflammatory response to nano- and microstructured hydroxyapatite.

The proliferation and activation of leukocytes upon contact with a biomaterial play a crucial role in the degree of inflammatory response, which may then determine the clinical failure or success of an implanted biomaterial. The aim of this study was to evaluate whether nano- and microstructured biomimetic hydroxyapatite substrates can influence the growth and activation of macrophage-like cells. Hydroxyapatite substrates with different crystal morphologies consisting of an entangled network of plate-like and needle-like crystals were evaluated. Macrophage proliferation was evaluated on the material surface (direct contact) and also in extracts i.e. media modified by the material (indirect contact). Additionally, the effect of supplementing the extracts with calcium ions and/or proteins was investigated. Macrophage activation on the substrates was evaluated by quantifying the release of reactive oxygen species and by morphological observations. The results showed that differences in the substrate’s microstructure play a major role in the activation of macrophages as there was a higher release of reactive oxygen species after culturing the macrophages on plate-like crystals substrates compared to the almost non-existent release on needle-like substrates. However, the difference in macrophage proliferation was ascribed to different ionic exchanges and protein adsorption/retention from the substrates rather than to the texture of materials.

Reducing the Foreign Body Reaction by Surface Modification with Collagen/Hyaluronic Acid Multilayered Films

Biological response against foreign implants often leads to encapsulation, possibly resulting in malfunction of implants devices. The aim of this study was to reduce the foreign body reaction by surface modification of biomaterials through layer-by-layer deposition of type I collagen (COL)/hyaluronic acid (HA) multilayer films. Polydimethylsiloxane (PDMS) samples were coated with alternative COL and HA layers with different layers. We found that the in vitro adhesion, proliferation, and activation of macrophage-like cells were greatly decreased by COL/HA multilayered deposition. The PDMS samples modified with 20 bilayers of COL/HA were implanted in rats for 3 weeks, and the thickness of encapsulation surrounding the samples was decreased by 29–57% compared to the control unmodified PDMS. This study demonstrates the potential of COL/HA multilayer films to reduce foreign body reaction.

Cartilage-reactive T cells in rheumatoid synovium.

Rheumatoid arthritis (RA) is an inflammatory polyarthritis genetically linked to HLA-DR4 and related haplotypes. RA synovial tissue is characterized by T cell infiltration and activation of macrophage-like cells, strongly implicating a T cell-antigen-presenting cell (APC) interaction in RA pathogenesis. To investigate the nature of the antigens driving the T cell response, synovial tissue was obtained from a patient with chronic RA and T cells were enriched. These T cells were stimulated by endogenous APC from the same synovial tissue. The T cell lines were subsequently evaluated for responsiveness to autologous APC and cartilage antigens. Specific proliferative responses to autologous APC which were enhanced by cartilage extract were seen. Immunomagnetic bead selection and RT-PCR was used to identify TCR alphabeta pairs which appeared to respond to antigen(s) in the cartilage extract. T cell clones derived from the same joint were shown to release IL-2 in response to the cartilage extract and expressed a related TCR. With these experiments we have shown direct evidence that autoreactive T cells are found within the inflamed rheumatoid synovium and, further, that the antigens driving these T cells are cartilage derived. Since the antigens recognized by these populations of T cells are found within cartilage our data provides evidence that RA pathology could be related to a self-driven autoimmune response to cartilage proteins.