Rhegmatogenous retinal detachment (RRD) is a serious condition that can cause blindness without surgical treatment. RRD occurs when a retinal tear or hole allows fluid to accumulate below the retinal ...surface, causing the retina to separate from the underlying layers. RRD is difficult to treat because each case is unique, varying with the location, size, and duration of the detachment, as well as patient age. The first successful methods to reattach the retina in RRD used thermocautery to repair the detachment. Many renowned ophthalmologists continued to study RRD and developed many new surgical approaches, notably: scleral buckling (SB), in which a silicone band is placed around the eye to reduce traction on the retina caused by the vitreous humor that fills the eye; pars plana vitrectomy (PPV), which eliminates traction on the retina by removing the vitreous; and pneumatic retinopexy (PR), in which the retina is reattached by pushing it back into place with an expanding gas bubble injected into the eye. However, no consensus has been reached on which approach is ideal. Furthermore, recent surgical and non-surgical breakthroughs, such as artificial vitreous substitutes and neuroprotective drugs, must also be considered. Thus, this review provides a guide for ocular specialists and non-specialists on the historical background of RRD, summarizes the three current main techniques (SB, PR and PPV) compares these three techniques, and provides an overview of new technologies that promise to greatly improve outcomes after RRD surgery.
Angiogenesis plays a critical role in many diseases, including macular degeneration. At present, the pathological mechanisms remain unclear while appropriate models dissecting regulation of ...angiogenic processes are lacking. We propose an in vitro angiogenesis process and test it by examining the co-culture of human retinal pigmental epithelial cells (ARPE-19) and human umbilical vein endothelial cells (HUVEC) inside a microfluidic device. From characterisation of the APRE-19 monoculture, the tight junction protein (ZO-1) was found on the cells cultured in the microfluidic device but changes in the medium conditions did not affect the integrity of monolayers found in the permeability tests. Vascular endothelial growth factor (VEGF) secretion was elevated under low glucose and hypoxia conditions compared to the control. After confirming the angiogenic ability of HUVEC, the cell-cell interactions were analyzed under lowered glucose medium and chemical hypoxia by exposing ARPE-19 cells to cobalt (II) chloride (CoCl
). Heterotypic interactions between ARPE-19 and HUVEC were observed, but proliferation of HUVEC was hindered once the monolayer of ARPE-19 started breaking down. The above characterisations showed that alterations in glucose concentration and/or oxygen level as induced by chemical hypoxia causes elevations in VEGF produced in ARPE-19 which in turn affected directional growth of HUVEC.
The administration of anti-vascular endothelial growth factor drugs in the posterior eye segment with sustained release through less invasive methods is a challenge in the treatment of age-related ...macular disease. We developed a flexible capsule device using porous poly(dimethylsiloxane) (PDMS) that was able to release ranibizumab. The porous PDMS sheet was fabricated by salt-leaching of a micro-sectioned PDMS sheet containing salt microparticles. Observation with scanning electron microscopy revealed that the pore densities could be adjusted by the concentration of salt. The in vitro release study showed that the release rate of fluorescein isothiocyanate-tagged albumin could be adjusted based on the pore density of the porous PDMS sheet. Ranibizumab could be released in a sustained-release manner for 16 weeks. The device was implanted on the sclera; its efficacy in terms of the suppression of laser-induced choroidal neovascularization (CNV) in rats was compared with that of monthly intravitreal injections of ranibizumab. At 8 and 18 weeks after implantation, the CNV area was significantly reduced in rats that received the ranibizumab-releasing device compared with those that received the placebo device. However, although monthly intravitreal injections of ranibizumab reduced CNV for 8 weeks, this reduction was not sustained for 18 weeks. In conclusion, we demonstrated a novel controlled-release device using a porous PDMS sheet that could suppress CNV via a less invasive transscleral route versus intravitreal injections. This device may also reduce the occurrence of side effects associated with frequent intravitreal injections.
Graphical Abstract
We evaluated several hemodynamic parameters for the prediction of rupture in a data set of initially unruptured aneurysms, including aneurysms that ruptured during follow-up observation.
Aneurysm ...geometry was extracted from CT angiographic images and analyzed using a mathematical formula for fluid flow under pulsatile blood flow conditions. Fifty side-wall internal carotid posterior communicating artery aneurysms and 50 middle cerebral artery bifurcation aneurysms of medium size were investigated for energy loss, pressure loss coefficient, wall shear stress, and oscillatory shear index. During follow-up observation, 6 internal carotid posterior communicating artery and 7 middle cerebral artery aneurysms ruptured (44 and 43 remained unruptured, respectively, with the same location and a similar size as the ruptured cases).
A significant difference in the minimum wall shear stress between aneurysms that ruptured and those that remained unruptured was noted only in internal carotid artery aneurysms (P<0.001). Energy loss showed a higher tendency in ruptured aneurysms but statistically not significant. For pressure loss coefficient, a significant difference was noted in both internal carotid artery (P=0.0046) and middle cerebral artery (P<0.001) aneurysms.
Pressure loss coefficient may be a potential parameter to predict future rupture of unruptured aneurysms.
A simulation model was developed to better understand the mechanisms of brain injuries in sports. A three-dimensional model comprising approximately 1.22 million elements was constructed from cranial ...computed tomography images of adult male volunteers by the voxel method. To simulate contact sports that permit actions such as tackling, a sinusoidal wave with duration of 10 ms and maximum acceleration of 2000 m/s2 was applied to the lowest point of the model to apply rotational acceleration to the head from different directions. The von Mises stress was then observed at five points in the coronal plane of the brain: cingulate gyrus (CG), corpus callosum (CC), brain stem (BS), lateral temporal lobe (LT), and medial temporal lobe (MT). LS-DYNA universal finite element analysis software with explicit time integration was used for the analysis. Concentrations of stress started to appear in the CC and BS at 10 ms post-impact, after which they also became evident in the CG and MT. The maximum changes in stress at each location occurred 10–15 ms post-impact. The von Mises stress was 9–14 kPa in the CG, 8–24 kPa in the CC, 12–24 kPa in the BS, 7–12 kPa in the LT, and 12–18 kPa in the MT. The highest stress in every part of the brain occurred after lateral impact, followed by oblique impact and sagittal impact. Such simulations may help elucidate the mechanisms of brain injuries in sports and help develop measures to prevent chronic traumatic encephalopathy.
To investigate the relationship between aqueous flare, visual function and macular structures in retinitis pigmentosa (RP).
Clinical data from 123 patients with RP (227 eyes), 35 patients ...with macular dystrophy (68 eyes) and 148 controls (148 eyes) were analysed. The differences in aqueous flare between clinical entities and the correlation between aqueous flare (measured with a laser flare cell meter) versus visual acuity, visual field area (Goldmann perimetry) and macular thickness (optical coherence tomography) in patients with RP were determined. Influence of selected clinical data on flare was assessed using linear mixed-effects model.
Aqueous flare was higher in patients with RP than patients with macular dystrophy or controls (p=7.49×E-13). Aqueous flare was correlated with visual field area (R=-0.379, p=3.72×E-9), but not with visual acuity (R=0.083, p=0.215). Macular thickness (R=0.234, p=3.74×E-4), but not foveal thickness (R=0.122, p=0.067), was positively correlated with flare. Flare was not affected by the presence of macular complications. All these associations were maintained when the right and the left eyes were assessed separately. Analysis by linear mixed-effects model revealed that age (p=8.58×E-5), visual field area (p=8.01×E-7) and average macular thickness (p=0.037) were correlated with flare.
Aqueous flare and visual field area were correlated in patients with RP. Aqueous flare may reflect the degree of overall retinal degeneration more closely than the local foveal impairment.
Retinal cells are irreparably damaged by diseases such as age-related macular degeneration (AMD). A promising method to restore partial or whole vision is through cell-based transplantation to the ...damaged location. However, cell transplantation using conventional vitreous surgery is an invasive procedure that may induce infections and has a high failure rate of cell engraftment. In this study, we describe the fabrication of a biodegradable composite nanosheet used as a substrate to support retinal pigment epithelial (RPE-J) cells, which can be grafted to the sub-retinal space using a minimally invasive approach. The nanosheet was fabricated using polycaprolactone (PCL) and collagen in 80:20 weight ratio, and had size of 200 µm in diameter and 300 nm in thickness. These PCL/collagen nanosheets showed excellent biocompatibility and mechanical strength
. Using a custom designed 27-gauge glass needle, we successfully transplanted an RPE-J cell loaded nanosheet into the sub-retinal space of a rat model with damaged photoreceptors. The cell loaded nanosheet did not trigger immunological reaction within 2 weeks of implantation and restored the retinal environment. Thus, this composite PCL/collagen nanosheet holds great promise for organized cell transplantation, and the treatment of retinal diseases.
Fatty acid‐binding protein 7 (FABP7), one of the fatty acid (FA) chaperones involved in the modulation of intracellular FA metabolism, is highly expressed in glioblastoma, and its expression is ...associated with decreased patients' prognosis. Previously, we demonstrated that FABP7 requires its binding partner to exert its function and that a mutation in the FA‐binding site of FABP7 affects tumour biology. Here, we explored the role of FA ligand binding for FABP7 function in tumour proliferation and examined the mechanism of FABP7 and ligand interaction in tumour biology. We discovered that among several FA treatment, oleic acid (OA) boosted cell proliferation of FABP7‐expressing cells. In turn, OA increased FABP7 nuclear localization, and the accumulation of FABP7–OA complex in the nucleus induced the formation of nuclear lipid droplet (nLD), as well as an increase in colocalization of nLD with promyelocytic leukaemia (PML) nuclear bodies. Furthermore, OA increased mRNA levels of proliferation‐related genes in FABP7‐expressing cells through histone acetylation. Interestingly, these OA‐boosted functions were abrogated in FABP7‐knockout cells and mutant FABP7‐overexpressing cells. Thus, our findings suggest that FABP7–OA intracellular interaction may modulate nLD formation and the epigenetic status thereby enhancing transcription of proliferation‐regulating genes, ultimately driving tumour cell proliferation.
FABP7 binds with oleic acids (OAs), and the complex translocates into the nucleus in glioma cells. This leads to nuclear LD (nLD) formation through increased TAG synthesis and PML expression. Subsequent promotion of histone acetylation upregulates the expression of proliferation regulatory genes, which ultimately drives proliferation in glioma cells. These findings propose a newly identified modulatory mechanism in tumour biology by nLD formation regulated by OA–FABP7 interaction.
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