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The authors originally published this article under the incorrect license type; this has now been corrected and is published under the CC-BY license.
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Cell transplantation is a potential strategy for treating blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells are able to migrate into the adult retina and differentiate to acquire the specialized morphological features of mature photoreceptor cells, the fundamental question remains whether transplantation of photoreceptor cells can actually improve vision. Here we provide evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1−/− mice, which lack rod function and are a model of congenital stationary night blindness. We show that transplanted rod precursors form classic triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. The newly integrated photoreceptor cells are light-responsive with dim-flash kinetics similar to adult wild-type photoreceptors. By using intrinsic imaging under scotopic conditions we demonstrate that visual signals generated by transplanted rods are projected to higher visual areas, including V1. Moreover, these cells are capable of driving optokinetic head tracking and visually guided behaviour in the Gnat1−/− mouse under scotopic conditions. Together, these results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.
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Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Células Fotorreceptoras Retinianas Bastonetes/transplante , Visão Ocular/fisiologia , Animais , Subunidades alfa de Proteínas de Ligação ao GTP/deficiência , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Luz , Aprendizagem em Labirinto , Camundongos , Células Bipolares da Retina/ultraestrutura , Células Horizontais da Retina/ultraestrutura , Células Fotorreceptoras Retinianas Bastonetes/citologia , Células Fotorreceptoras Retinianas Bastonetes/efeitos da radiação , Transducina/deficiência , Transducina/genética , Visão Ocular/efeitos da radiação , Córtex Visual/fisiologia , Córtex Visual/efeitos da radiaçãoRESUMO
Soil salinization is one of the major environmental problems facing agricultural lands in arid and semiarid areas of the world because of its detrimental impacts on agricultural production and on the sustainable development of land resources. Hence, predicting soil salinity is essential to avoiding further soil degradation. The present study is intended to develop a model for predicting soil salinity in soils around Idku Lake by using remote sensing and geographic information system techniques. This lake is a shallow brackish basin located in the western part of the Nile Delta. For this purpose, Landsat 8-OLI images and shuttle radar topography mission 1Arc-Second Digital Elevation Model data were utilized in this research. A total of 91 surface samples were collected across the study area at a depth between 0 and 30 cm and were analyzed via traditional laboratory analysis methods. Five environmental parameters were used in the design of the soil salinity model. A pairwise comparison matrix was used to calculate the factor weight value for each of the layers. A linear regression model was used to plot the relationship between the EC value and raster value of the salinity map derived from the overlay model. According to the results obtained from a pairwise comparison of the factor layers, water table level was the greatest influential factor of soil salinity, followed by landforms. The validation of the model demonstrated a high degree of correlation (R2 = 0.72) between the measured EC values and the salinity values derived from the model. Furthermore, this model could be a useful tool for predicting soil salinity with a suitable validation.
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Monitoramento Ambiental/métodos , Sistemas de Informação Geográfica , Tecnologia de Sensoriamento Remoto , Salinidade , Solo/química , Agricultura , Egito , Lagos/química , RiscoRESUMO
The retinal pigment epithelium (RPE) interacts closely with photoreceptors to maintain visual function. In degenerative diseases such as Stargardt disease and age-related macular degeneration, the leading cause of blindness in the developed world, RPE cell loss is followed by photoreceptor cell death. RPE cells can proliferate under certain conditions, suggesting an intrinsic regenerative potential, but so far this has not been utilised therapeutically. Here, we used E2F2 to induce RPE cell replication and thereby regeneration. In both young and old (2 and 18 month) wildtype mice, subretinal injection of non-integrating lentiviral vector expressing E2F2 resulted in 47% of examined RPE cells becoming BrdU positive. E2F2 induced an increase in RPE cell density of 17% compared with control vector-treated and 14% compared with untreated eyes. We also tested this approach in an inducible transgenic mouse model of RPE loss, generated through activation of diphtheria toxin-A gene. E2F2 expression resulted in a 10-fold increase in BrdU uptake and a 34% increase in central RPE cell density. Although in mice this localised rescue is insufficiently large to be demonstrable by electroretinography, a measure of massed retinal function, these results provide proof-of-concept for a strategy to induce in situ regeneration of RPE for the treatment of RPE degeneration.
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Fator de Transcrição E2F2/genética , Técnicas de Transferência de Genes , Terapia Genética , Degeneração Macular/terapia , Epitélio Pigmentado da Retina/fisiopatologia , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Proliferação de Células/genética , Toxina Diftérica/genética , Modelos Animais de Doenças , Vetores Genéticos , Camundongos , Camundongos Transgênicos , Fragmentos de Peptídeos/genética , Regeneração , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/metabolismoRESUMO
The X-linked RP3 gene codes for the ciliary protein RPGR and accounts for over 10% of inherited retinal degenerations. The critical RPGR-ORF15 splice variant contains a highly repetitive purine-rich linker region that renders it unstable and difficult to adapt for gene therapy. To test the hypothesis that the precise length of the linker region is not critical for function, we evaluated whether adeno-associated virus-mediated replacement gene therapy with a human ORF15 variant containing in-frame shortening of the linker region could reconstitute RPGR function in vivo. We delivered human RPGR-ORF15 replacement genes with deletion of most (314 codons, 'short form') or 1/3 (126 codons, 'long form') of the linker region to Rpgr null mice. Human RPGR-ORF15 expression was detected post treatment with both forms of ORF15 transgenes. However, only the long form correctly localized to the connecting cilia and led to significant functional and morphological rescue of rods and cones. Thus the highly repetitive region of RPGR is functionally important but that moderate shortening of its length, which confers the advantage of added stability, preserves its function. These findings provide a theoretical basis for optimizing replacement gene design in clinical trials for X-linked RP3.
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Dependovirus/genética , Proteínas do Olho/genética , Terapia Genética , Retinose Pigmentar/terapia , Processamento Alternativo , Animais , Modelos Animais de Doenças , Receptor Quinase 1 Acoplada a Proteína G/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Retinose Pigmentar/genéticaRESUMO
Leber congenital amaurosis is a group of inherited retinal dystrophies that cause severe sight impairment in childhood; RPE65-deficiency causes impaired rod photoreceptor function from birth and progressive impairment of cone photoreceptor function associated with retinal degeneration. In animal models of RPE65 deficiency, subretinal injection of recombinant adeno-associated virus (AAV) 2/2 vectors carrying RPE65 cDNA improves rod photoreceptor function, and intervention at an early stage of disease provides sustained benefit by protecting cone photoreceptors against retinal degeneration. In affected humans, administration of these vectors has resulted to date in relatively modest improvements in photoreceptor function, even when retinal degeneration is comparatively mild, and the duration of benefit is limited by progressive retinal degeneration. We conclude that the demand for RPE65 in humans is not fully met by current vectors, and predict that a more powerful vector will provide more durable benefit. With this aim we have modified the original AAV2/2 vector to generate AAV2/5-OPTIRPE65. The new configuration consists of an AAV vector serotype 5 carrying an optimized hRPE65 promoter and a codon-optimized hRPE65 gene. In mice, AAV2/5-OPTIRPE65 is at least 300-fold more potent than our original AAV2/2 vector.
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Dependovirus/genética , Terapia Genética/métodos , Vetores Genéticos/genética , Amaurose Congênita de Leber/terapia , cis-trans-Isomerases/genética , Células 3T3 , Animais , Feminino , Vetores Genéticos/administração & dosagem , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Coelhos , cis-trans-Isomerases/metabolismoRESUMO
The eastern Mediterranean region is a vital hub for oil transportation and production because of its strategic location between Europe, Asia, and Africa. But its unique attributes, including narrow shipping routes, heavy marine traffic, and proximity to vulnerable ecosystems, render it particularly susceptible to accidental oil spills. In this research, an oil spill detection model, along with bathymetric and oceanographic parameters, was used to track oil spills that occurred at the Syrian Baniyas Station in the Eastern Mediterranean on August 23, 2021. Furthermore, the study employed a pairwise comparison matrix (PWCM) to assess the relative importance of wind speed and direction, water depth, and sea surface temperature (SST) in the dispersion of oil spills. Analysis of Sentinel-1 data obtained prior to, during, and after the incident revealed the accumulation of oil slicks along the Syrian coast from Baniyas to Latakia for up to twenty days. The spilled oil reached the coast of Cyprus six days after the incident. The study determined that wind speed and direction played a critical role in the dispersion of spilled oil, while water depth and SST were comparatively less significant factors in this process. The overall accuracy (OA) and Kappa coefficient (KC) for land, water, and oil slick classes derived from the random forest (RF) algorithm ranged from 90 % to 98 % and from 0.86 to 0.98, respectively. The spread of oil slicks at the incident location was revealed by the decorrelation stretch and band ratios of Sentinel-2 MultiSpectral Instrument (MSI) data. The accidental oil spill could have negative effects on the organic carbon cycle, chlorophyll production, and ecosystem productivity. It is essential to consider the vulnerability of specific regions in the Eastern Mediterranean to oil spills when developing adaptation strategies.
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Poluição por Petróleo , Poluição por Petróleo/análise , Ecossistema , Acidentes , Água/análise , Chipre , Monitoramento AmbientalRESUMO
Recent clinical trials of retinal pigment epithelium gene (RPE65) supplementation therapy in Leber congenital amaurosis type 2 patients have demonstrated improvements in rod and cone function, but it may be some years before the effects of therapy on photoreceptor survival become apparent. The Rpe65-deficient dog is a very useful pre-clinical model in which to test efficacy of therapies, because the dog has a retina with a high degree of similarity to that of humans. In this study, we evaluated the effect of RPE65 gene therapy on photoreceptor survival in order to predict the potential benefit and limitations of therapy in patients. We examined the retinas of Rpe65-deficient dogs after RPE65 gene therapy to evaluate the preservation of rods and cone photoreceptor subtypes. We found that gene therapy preserves both rods and cones. While the moderate loss of rods in the Rpe65-deficient dog retina is slowed by gene therapy, S-cones are lost extensively and gene therapy can prevent that loss, although only within the treated area. Although LM-cones are not lost extensively, cone opsin mislocalization indicates that they are stressed, and this can be partially reversed by gene therapy. Our results suggest that gene therapy may be able to slow cone degeneration in patients if intervention is sufficiently early and also that it is probably important to treat the macula in order to preserve central function.
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Amaurose Congênita de Leber/terapia , Células Fotorreceptoras Retinianas Cones , Células Fotorreceptoras Retinianas Bastonetes , cis-trans-Isomerases/genética , Animais , Sobrevivência Celular/genética , Modelos Animais de Doenças , Cães , Terapia Genética , Amaurose Congênita de Leber/genética , Amaurose Congênita de Leber/patologia , Retina/efeitos dos fármacos , Retina/patologia , Células Fotorreceptoras Retinianas Cones/efeitos dos fármacos , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Bastonetes/efeitos dos fármacos , Células Fotorreceptoras Retinianas Bastonetes/patologia , cis-trans-Isomerases/administração & dosagem , cis-trans-Isomerases/deficiênciaRESUMO
The gene Prph2 encodes a photoreceptor-specific membrane glycoprotein, peripherin-2 (also known as peripherin/rds), which is inserted into the rims of photoreceptor outer segment discs in a complex with rom-1 (ref. 2). The complex is necessary for the stabilization of the discs, which are renewed constantly throughout life, and which contain the visual pigments necessary for photon capture. Mutations in Prph2 have been shown to result in a variety of photoreceptor dystrophies, including autosomal dominant retinitis pigmentosa and macular dystrophy. A common feature of these diseases is the loss of photoreceptor function, also seen in the retinal degeneration slow (rds or Prph2 Rd2/Rd2) mouse, which is homozygous for a null mutation in Prph2. It is characterized by a complete failure to develop photoreceptor discs and outer segments, downregulation of rhodopsin and apoptotic loss of photoreceptor cells. The electroretinograms (ERGs) of Prph2Rd2/Rd2 mice have greatly diminished a-wave and b-wave amplitudes, which decline to virtually undetectable concentrations by two months. Subretinal injection of recombinant adeno-associated virus (AAV) encoding a Prph2 transgene results in stable generation of outer segment structures and formation of new stacks of discs containing both perpherin-2 and rhodopsin, which in many cases are morphologically similar to normal outer segments. Moreover, the re-establishment of the structural integrity of the photoreceptor layer also results in electrophysiological correction. These studies demonstrate for the first time that a complex ultrastructural cell defect can be corrected both morphologically and functionally by in vivo gene transfer.
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Terapia Genética , Proteínas de Filamentos Intermediários/fisiologia , Glicoproteínas de Membrana , Proteínas do Tecido Nervoso/fisiologia , Células Fotorreceptoras Retinianas Cones/fisiopatologia , Células Fotorreceptoras Retinianas Bastonetes/fisiopatologia , Retinose Pigmentar/fisiopatologia , Retinose Pigmentar/terapia , Animais , Linhagem Celular , Cricetinae , Modelos Animais de Doenças , Terapia Genética/métodos , Proteínas de Filamentos Intermediários/genética , Camundongos , Camundongos Endogâmicos CBA , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Periferinas , Células Fotorreceptoras Retinianas Cones/metabolismo , Células Fotorreceptoras Retinianas Cones/ultraestrutura , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/ultraestrutura , Retinose Pigmentar/genética , Retinose Pigmentar/metabolismo , Rodopsina/metabolismoRESUMO
Substantial advances in our understanding of lentivirus lifecycles and their various constituent proteins have permitted the bioengineering of lentiviral vectors now considered safe enough for clinical trials for both lethal and non-lethal diseases. They possess distinct properties that make them particularly suitable for gene delivery in ophthalmic diseases, including high expression, consistent targeting of various post-mitotic ocular cells in vivo and a paucity of associated intraocular inflammation, all contributing to their ability to mediate efficient and stable intraocular gene transfer. In this review, the intraocular tropisms and therapeutic applications of both primate and non-primate lentiviral vectors, and how the unique features of the eye influence these, are discussed. The feasibility of therapeutic targeting using these vectors in animal models of both anterior and posterior ophthalmic disorders has been established, and has, in combination with substantial progress in enhancing lentiviral vector bio-safety over the past two decades, paved the way for the first human ophthalmic clinical trials using lentivirus-based gene transfer vectors.
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Neovascularização de Coroide/genética , Técnicas de Transferência de Genes , Glaucoma/genética , Lentivirus , Degeneração Retiniana/genética , Animais , Neovascularização de Coroide/terapia , Modelos Animais de Doenças , Expressão Gênica , Terapia Genética , Vetores Genéticos/administração & dosagem , Glaucoma/terapia , Humanos , Degeneração Retiniana/terapiaRESUMO
Over the last decade, gene supplementation therapy for inherited retinal degeneration has come of age. Early proof-of-concept studies in animal models of disease showed modest, but genuine improvements in retinal function and/or survival. Further development of the vectors used for gene transfer to the retina has led to better treatment efficacy in a wide variety of animal models, leading in 2008 to the initiation of three clinical trials for Leber congenital amaurosis caused by retinal pigment epithelium 65 deficiency. The results from these trials suggest that the treatment of inherited retinal dystrophy by gene therapy can be safe and effective. Here, we examine the progress of gene supplementation therapy in the retina, and discuss the potential for using gene therapy to treat different forms of inherited retinal degeneration.
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Terapia Genética , Amaurose Congênita de Leber/terapia , Retina/patologia , Distrofias Retinianas/genética , Distrofias Retinianas/terapia , Animais , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Genes Recessivos , Humanos , Amaurose Congênita de Leber/genética , Células Fotorreceptoras/metabolismo , Células Fotorreceptoras/patologiaRESUMO
Insertional mutagenesis following gene therapy with gammaretroviral vectors can cause the development of lymphoproliferation in children with X-linked severe combined immunodeficiency. In experimental studies, recombinant adeno-associated virus (rAAV) vectors have also been reported to increase susceptibility to carcinogenesis. The possibility of vector-induced transformation in quiescent ocular cells is probably significantly lower than in mitotically active cells, but given the increasing number of clinical applications of rAAV and lentiviral vectors for ocular disease, a specific assessment of their oncogenic potential in the eye is important. In this study, we investigated the effect of rAAV2/2 and integrating HIV-1 vectors upon the incidence of ocular neoplasia in p53 tumour-suppressor gene-knockout (p53(-/-)) mice, which are highly susceptible to intraocular malignant transformation. Subretinal injections of high titre rAAV2/2 or integrating HIV-1 vectors induced no tumours in p53(-/-) or p53(+/-) animals, nor significantly affected their natural longevity. We conclude that any insertional events arising from subretinal delivery of these vectors appear insufficient to cause intraocular malignancy, even in highly susceptible animals. These findings support the continued development of these vectors for ocular applications.
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Dependovirus/genética , Técnicas de Transferência de Genes/efeitos adversos , Vetores Genéticos/efeitos adversos , Lentivirus/genética , Proteína Supressora de Tumor p53/genética , Animais , Transformação Celular Neoplásica/genética , Eletrorretinografia , Neoplasias Oculares/genética , Técnicas de Inativação de Genes , Terapia Genética , Vetores Genéticos/administração & dosagem , Proteínas de Fluorescência Verde , Camundongos , Retina , Proteína Supressora de Tumor p53/deficiênciaRESUMO
Retinal degenerative disease causing loss of photoreceptor cells is the leading cause of untreatable blindness in the developed world, with inherited degeneration affecting 1 in 3000 people. Visual acuity deteriorates rapidly once the cone photoreceptors die, as these cells provide daylight and colour vision. Here, in proof-of-principle experiments, we demonstrate the feasibility of cone photoreceptor transplantation into the wild-type and degenerating retina of two genetic models of Leber congenital amaurosis, the Crb1(rd8/rd8) and Gucy2e(-/-) mouse. Crx-expressing cells were flow-sorted from the developing retina of CrxGFP transgenic mice and transplanted into adult recipient retinae; CrxGFP is a marker of cone and rod photoreceptor commitment. Only the embryonic-stage Crx-positive donor cells integrated within the outer nuclear layer of the recipient and differentiated into new cones, whereas postnatal cells generated a 10-fold higher number of rods compared with embryonic-stage donors. New cone photoreceptors displayed unambiguous morphological cone features and expressed mature cone markers. Importantly, we found that the adult environment influences the number of integrating cones and favours rod integration. New cones and rods were observed in ratios similar to that of the host retina (1:35) even when the transplanted population consisted primarily of cone precursors. Cone integration efficiency was highest in the cone-deficient Gucy2e(-/-) retina suggesting that cone depletion creates a more optimal environment for cone transplantation. This is the first comprehensive study demonstrating the feasibility of cone transplantation into the adult retina. We conclude that flow-sorted embryonic-stage Crx-positive donor cells have the potential to replace lost cones, as well as rods, an important requirement for retinal disease therapy.
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Transplante de Células/métodos , Amaurose Congênita de Leber/terapia , Células Fotorreceptoras Retinianas Cones/transplante , Células Fotorreceptoras Retinianas Bastonetes/transplante , Animais , Cegueira/terapia , Diferenciação Celular , Modelos Animais de Doenças , Embrião de Mamíferos , Camundongos , Camundongos Transgênicos , Retina/citologiaRESUMO
Retinal degenerative diseases are a major cause of untreatable blindness. Stem cell therapy to replace lost photoreceptors represents a feasible future treatment. We previously demonstrated that postmitotic photoreceptor precursors expressing an NrlGFP transgene integrate into the diseased retina and restore some light sensitivity. As genetic modification of precursor cells derived from stem cell cultures is not desirable for therapy, we have tested cell selection strategies using fluorochrome-conjugated antibodies recognizing cell surface antigens to sort photoreceptor precursors. Microarray analysis of postnatal NrlGFP-expressing precursors identified four candidate genes encoding cell surface antigens (Nt5e, Prom1, Podxl, and Cd24a). To test the feasibility of using donor cells isolated using cell surface markers for retinal therapy, cells selected from developing retinae by fluorescence-activated cell sorting based on Cd24a expression (using CD24 antibody) and/or Nt5e expression (using CD73 antibody) were transplanted into the wild-type or Crb1(rd8/rd8) or Prph2(rd2/rd2) mouse eye. The CD73/CD24-sorted cells migrated into the outer nuclear layer, acquired the morphology of mature photoreceptors and expressed outer segment markers. They showed an 18-fold higher integration efficiency than that of unsorted cells and 2.3-fold higher than cells sorted based on a single genetic marker, NrlGFP, expression. These proof-of-principle studies show that transplantation competent photoreceptor precursor cells can be efficiently isolated from a heterogeneous mix of cells using cell surface antigens without loss of viability for the purpose of retinal stem cell therapy. Refinement of the selection of donorphotoreceptor precursor cells can increase the number of integrated photoreceptor cells,which is a prerequisite for the restoration of sight.
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Antígenos de Superfície/biossíntese , Células Fotorreceptoras Retinianas Bastonetes/transplante , Células-Tronco/citologia , Animais , Diferenciação Celular , Perfilação da Expressão Gênica , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Retina/citologia , Células Fotorreceptoras Retinianas Bastonetes/citologia , Células Fotorreceptoras Retinianas Bastonetes/imunologia , Células-Tronco/imunologiaRESUMO
Transfer of cDNA to corneal endothelial cells has been demonstrated in cell monolayers in vitro, in endothelium of whole thickness corneas ex vivo and following intracameral injection. Studies examining the feasibility and optimal methods for gene transfer to the cornea have used viral and non-viral vectors, initially histochemical or fluorescent marker genes, and in endothelium of numerous species ranging from mouse to man. As the feasibility of genetic modification of corneal endothelial cells has been successfully demonstrated in a number of cell culture and animal models, there is significant potential for gene transfer in the treatment of human corneal endothelial disease. The two most widely studied applications of gene transfer to endothelium are (i) transduction of immunomodulatory genes to donor corneal endothelium prior to transplantation as a strategy to delay allogeneic rejection and (ii) modulation of apoptosis or induction of replication in human corneal endothelial cells to increase cell density. Although continued improvements in vectors for gene transfer will improve the efficacy and safety of gene therapy, more detailed understanding of the altered biology of endothelium in disease will be necessary to allow selection of appropriate targets for a gene-based treatment approach.
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Córnea/irrigação sanguínea , Doenças da Córnea/terapia , Células Endoteliais/metabolismo , Técnicas de Transferência de Genes , Terapia Genética/métodos , Animais , Doenças da Córnea/genética , Doenças da Córnea/metabolismo , Doenças da Córnea/patologia , Transplante de Córnea/efeitos adversos , Células Endoteliais/patologia , Vetores Genéticos , Rejeição de Enxerto/genética , Rejeição de Enxerto/prevenção & controle , HumanosRESUMO
Photoreceptor loss causes irreversible blindness in many retinal diseases. Repair of such damage by cell transplantation is one of the most feasible types of central nervous system repair; photoreceptor degeneration initially leaves the inner retinal circuitry intact and new photoreceptors need only make single, short synaptic connections to contribute to the retinotopic map. So far, brain- and retina-derived stem cells transplanted into adult retina have shown little evidence of being able to integrate into the outer nuclear layer and differentiate into new photoreceptors. Furthermore, there has been no demonstration that transplanted cells form functional synaptic connections with other neurons in the recipient retina or restore visual function. This might be because the mature mammalian retina lacks the ability to accept and incorporate stem cells or to promote photoreceptor differentiation. We hypothesized that committed progenitor or precursor cells at later ontogenetic stages might have a higher probability of success upon transplantation. Here we show that donor cells can integrate into the adult or degenerating retina if they are taken from the developing retina at a time coincident with the peak of rod genesis. These transplanted cells integrate, differentiate into rod photoreceptors, form synaptic connections and improve visual function. Furthermore, we use genetically tagged post-mitotic rod precursors expressing the transcription factor Nrl (ref. 6) (neural retina leucine zipper) to show that successfully integrated rod photoreceptors are derived only from immature post-mitotic rod precursors and not from proliferating progenitor or stem cells. These findings define the ontogenetic stage of donor cells for successful rod photoreceptor transplantation.
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Terapia Baseada em Transplante de Células e Tecidos , Células Fotorreceptoras de Vertebrados/citologia , Células Fotorreceptoras de Vertebrados/transplante , Retina/citologia , Retina/patologia , Transplante de Células-Tronco , Animais , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Galinhas/genética , Luz , Camundongos , Células Fotorreceptoras de Vertebrados/efeitos da radiação , Retina/embriologia , Retina/efeitos da radiação , Degeneração Retiniana/patologia , Degeneração Retiniana/terapia , Sinapses/metabolismo , Fatores de TempoRESUMO
This study aims to monitor and map the oil spills which occurred from 2019 to 2021 along the northeastern portion of the Nile Delta using Sentinel-1 (SAR) and Sentinel-2 (MSI) data. The examination of VV polarized SAR-C images displayed the presence of the oil spills as dark spots of different sizes. These images were processed using the oil spills detection model in SNAP Toolbox. The oceanographic parameters that may influence the dispersal of oil spills were mapped using GIS technique. This study identified 29 oil spills during the study period in the research area. The largest spill was detected on February 23, 2019, and covered an area of about 10.5 km2. The band ratios and decorrelation stretch methods of available Sentinel-2 data confirmed the results of SAR-C data. The accuracy assessment of spills was achieved using Parallelepiped supervised classification model. The results demonstrated that the overall accuracy (OA) and Kappa coefficient (KC) for seawater, land, and oil spills classes were between 86% and 98% and 0.73% and 0.97%, respectively. The sensitivity zone of oil spills was higher in winter than in summer. This study proved the efficiency of VV polarized data of Sentinel-1 sensor for detection and mapping of oil spills. Several management strategies are needed in the offshore zone of the Nile Delta to limit oil pollution effects on the marine environment.
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Poluição por Petróleo , Monitoramento Ambiental/métodos , Oceanografia , Poluição por Petróleo/análise , Água do MarRESUMO
As photoreceptor cells die during retinal degeneration, the surrounding microenvironment undergoes significant changes that are increasingly recognized to play a prominent role in determining the efficacy of therapeutic interventions. Chondroitin Sulphate Proteoglycans (CSPGs) are a major component of the extracellular matrix that have been shown to inhibit neuronal regrowth and regeneration in the brain and spinal cord, but comparatively little is known about their expression in retinal degeneration. Here we provide a comprehensive atlas of the expression patterns of four individual CSPGs in three models of inherited retinal degeneration and wildtype mice. In wildtype mice, Aggrecan presented a biphasic expression, while Neurocan and Phosphacan expression declined dramatically with time and Versican expression remained broadly constant. In degeneration, Aggrecan expression increased markedly in Aipl1-/- and Pde6brd1/rd1, while Versican showed regional increases in the periphery of Rho-/- mice. Conversely, Neurocan and Phosphacan broadly decrease with time in all models. Our data reveal significant heterogeneity in the expression of individual CSPGs. Moreover, there are striking differences in the expression patterns of specific CSPGs in the diseased retina, compared with those reported following injury elsewhere in the CNS. Better understanding of the distinct distributions of individual CSPGs will contribute to creating more permissive microenvironments for neuro-regeneration and repair.