The vitreoretinal pharmacokinetic profiles were similar between nonvitrectomized and vitrectomized eyes. These observations are consistent with clinical findings of the DEX implant in patients who have undergone vitrectomy and should reduce concerns about the use of the DEX implant in eyes that have undergone vitrectomy.
The aim of this study was to determine whether retinal progenitor layer transplants form synaptic connections with the host and restore vision. Donor retinal sheets, isolated from E19 rat fetuses expressing human alkaline phosphatase (hPAP), were transplanted to the subretinal space of thirteen S334ter-3 rats with fast retinal degeneration at the age of 0.8 to 1.3 months. Recipients were sacrificed at the age of 1.6 to 11.8 months. Frozen sections were analyzed by confocal immunohistochemistry for the donor cell label hPAP and synaptic markers. Vibratome slices were stained for hPAP, and processed for EM. Visual responses were recorded by electrophysiology from the superior colliculus (SC) in 8 rats at the age of 5.3 to 11.8 months. -All recorded transplanted rats had restored or preserved visual responses in the SC corresponding to the transplant location in the retina, with thresholds between −2.8 and −3.4 log cd/m 2 . No such responses were found in age-matched S334ter-3 rats without transplant, or in sham surgeries. Donor cells and processes were identified in the host by light and electron microscopy. Transplant processes penetrated the inner host retina in spite of occasional glial barriers between transplant and host. Labeled neuronal processes were found in the host inner plexiform layer, and formed apparent synapses with unlabeled cells presumably of host origin. Conclusions: Synaptic connections between graft and host cells, together with visual responses from corresponding locations in the brain, support the hypothesis that functional connections develop following transplantation of retinal layers into rodent models of retinal degeneration.
Robust adaptive beamforming based on worst‐case performance optimization is investigated in this paper. It improves robustness against steering vector mismatches by the approach of diagonal loading. A closed‐form solution to optimal loading is derived after some approximations. Besides reducing the computational complexity, it shows how different factors affect the optimal loading. Based on this solution, a performance analysis of the beamformer is carried out. As a consequence, approximated closed‐form expressions of the source‐of‐interest power estimation and the output signal‐to‐interference‐plus‐noise ratio are presented in order to predict its performance. Numerical examples show that the proposed closed‐form expressions are very close to their actual values.
Near-space, defined as the region between 20 km and 100 km, offers many new capabilities that are not accessible to low earth orbit (LEO) satellites and airplanes, because it is above storm and not constrained by either the orbital mechanics of satellites or the high fuel consumption of airplanes. By placing radar transmitter/receiver in near-space platforms, many functions that are currently performed with satellites or airplanes could be performed in a cheaper way. Inspired by these advantages, this paper introduces several near-space vehicle-based radar configurations, such as near-space passive bistatic radar and high-resolution wide-swath (HRWS) synthetic aperture radar (SAR). Their potential applications, technical challenges and possible solutions are investigated. It is shown that near-space is a satisfactory solution to some specific remote sensing applications. Firstly, near-space passive bistatic radar using opportunistic illuminators offers a solution to persistent regional remote sensing, which is particularly interest for protecting homeland security or monitoring regional environment. Secondly, near-space provides an optimal solution to relative HRWS SAR imaging. Moreover, as motion compensation is a common technical challenge for the described radars, an active transponder-based motion compensation is also described.
Background Uveal melanoma (UVM) is the leading cause of eye-related mortality worldwide. This study aimed to explore the expression and prognostic value of matrix metalloproteinases (MMPs) in UVM. Methods Gene expression levels were obtained from the Gene Expression Omnibus (GEO) and Oncomine databases. Functional and pathway enrichment analyses were performed using the Metascape database. GeneMANIA was then applied to construct a protein-protein interaction network and identify the hub genes. Moreover, overall survival (OS) and disease-free survival (DFS) analysis for the hub genes was performed using the UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) online tool. Furthermore, TRRUST was used to predict the targets of the MMPs. Results Our results revealed that the transcriptional levels of MMP1, MMP9, MMP10, MMP11, MMP13, MMP14, and MMP17 were upregulated in UVM tissues compared to normal tissues. A protein-protein interaction (PPI) network was constructed and the top 50 hub genes were identified. The functions of MMPs and their neighboring proteins are mainly associated with ECM-receptor interaction, proteoglycans in cancer, the IL-17 signaling pathway, and microRNAs in cancer. Among the MMPs, MMP1/2/9/11/14/15/16/17/24 played significant roles in the progression of UVM from stage 3 to stage 4. We also found that the expression of MMP1, MMP2, MMP9, and MMP16 positively correlated with OS and DFS in patients with UVM. Additionally, 18 transcription factors associated with nine MMPs were identified. Conclusions The results of this study may provide potential biomarkers and targets for UVM. However, further studies are required to confirm these results.
Purpose: To evaluate retinal sheet transplants in S334ter-line-3 retinal degenerate rats by comparing visual responses recorded electrophysiologically with morphology based on light and electron microscopy. Methods: S334ter-line-3 retinal degenerate rats (n = 7) received retinal sheet transplants between postnatal days 28 and 31. The donor tissue was derived from transgenic embryonic day 19 (E19) rat retinae expressing human placental alkaline phosphatase (hPAP). Fresh retinal sheets were gently transplanted into the subretinal space of the left eye with the help of a custom-made implantation tool. Selected rats (n = 5) were subjected to electrophysiologic evaluation of visual responses from the superior colliculus about 84-121 days after surgery. Transplanted eyes were processed for light microscopy (LM) and electron microscopy (EM) evaluations.Results: All the transplanted rats that were evaluated for visual responses in the brain showed responses to very low light stimulation (−3.42 to −2.8 log cd/m 2 ) of the eye in a small area of the superior colliculus corresponding with the placement of the transplant in the host retina. Histologic evaluation showed that most of the transplants contained well-laminated areas with correct polarity in the subretinal space. Inside the transplant areas, rosettes of photoreceptors with inner and outer segments were found. In the laminated areas, the outer segments of photoreceptors were facing the host retinal pigment epithelium (RPE). Immunohistochemical evaluation of hPAP donor cells revealed areas with specific staining of the transplants in the subretinal space. Electron microscopic evaluation showed a glial demarcation membrane between the host and the transplant, however, processes originating from the transplant were observed inside the host retina. Conclusions: Sheets of E19 rat retina transplanted into the subretinal space of S334ter-line-3 rats survived without immune rejection and continued to show visual function when tested after 3 months. Well-developed photoreceptors and many synapse types were seen within the transplants. hPAP staining showed a certain degree of integration between the host retina and the transplant suggesting that transplanted photoreceptors contributed to the restored light sensitivity.
These authors contributed equally to this workPurpose: This study aimed to investigate the concentrations of cytokines and chemokines in diabetic macular edema (DME) eyes before and during therapy with the intravitreal injection of conbercept (IVC) and to identify associations with disease activity. Methods: The Bio-Plex ® 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) were used to detect cytokine levels in aqueous humour. Experimental aqueous humour samples were collected from 18 patients with DME at the same time that IVC was performed at baseline and at 1 month. Control aqueous humour samples were collected from 16 patients undergoing cataract surgery. Results: Significantly higher concentrations of vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), IL-8, eotaxin, granulocyte colony stimulating factor (G-CSF), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) were found in the aqueous humour of DME patients than cataract patients. One month after IVC, the intraocular concentrations of VEGF were significantly lower in the eyes of DME patients than at baseline. No other cytokines were significantly altered by conbercept therapy. Bestcorrected visual acuity (BCVA) slightly improved following IVC compared with that at baseline, although this difference was not significant, and central macular thickness (CMT) significantly decreased 1 month after IVC treatment. Conclusion: Angiogenic, inflammatory and growth factors are involved in the development of DME. With the exception of VEGF, IVC did not cause significant differences in any inflammatory cytokines or growth factors in DME patients. CMT is related to VEGF levels in aqueous humour.
The novel CAPN5 mutation (p.R289W) is responsible for the present ADNIV family. The mutant CAPN5 stimulated secretion and cleavage of SLIT2 fragments that may act as a bystander to regulate abnormal RPE cell proliferation for ADNIV.
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