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Retinal Cells (retinal + cell)
Terms modified by Retinal Cells Selected Abstracts1255: Diagnosis of retinoblastomaACTA OPHTHALMOLOGICA, Issue 2010L DESJARDINS Purpose Retinoblastoma is the most frequent malignant intra ocular tumors in childhood. The incidence is one out of 15000 to 18000 births. The median age at diagnosis is 24 months for unilateral and 12 months for bilateral. The genetic predisposition is autosomal do Methods In 1971 Knudson made the hypothesis that 2 genetic alterations in the same retinal cell were necessary. In bilateral disease there is one germline and one somatic mutation and in unilateral non hereditary, 2 somatic mutations. The Rb1gene is located on chromosome 13 q 1-4 . The Rb 1 protein is a pocket protein involved in the cell cycle regulation Results Most frequent symptoms are leukocoria and strabismus Later symptoms include heterochromia iridis,rubeosis, buphtalmia, pseudo hypopion, uveitis, inflammatory pseudo tumor and exophtalmia. Diagnosis of retinoblastoma is made by fundus examination. Imaging of the orbits and brain should be performed using MRI if possible. Ultrasonography with B and A scan is also useful as well as the use of Retcam . Differential diagnosis is sometimes easy when there is colobomas ,persistance of hyperplastic primary vitreous ,hamartomas or astrocytomas It can be difficult in cases of advanced Coats disease or when there is diffuse infiltrating retinoblastoma. Conclusion We have made a retrospective study on patients sent for suspicion of retinoblastoma in our institute from January 2003 to December 2005 If we compare this serie to the serie published in the literature we can say that the pourcentage of well diagnosed retinoblastoma is improving. We have found 16% of wrong diagnostics. There was 30% in the serie of Balmer in 1988 and 42% in the serie of Shields in 1991. The most frequent differential diagnosis reported in all series is Coats disease [source] Expression patterns of the opsin 5,related genes in the developing chicken retinaDEVELOPMENTAL DYNAMICS, Issue 7 2008Sayuri Tomonari Abstract The opsin gene family encodes G protein,coupled seven-transmembrane proteins that bind to a retinaldehyde chromophore for photoreception. It has been reported that opsin 5 is expressed in mammalian neural tissue, but its function has been elusive. As a first step to understand the function for opsin 5 in the developing eye, we searched for chicken opsin 5 -related genes in the genome by a bioinformatic approach and isolated opsin 5 cDNA fragments from the embryonic retina by RT-PCR. We found that there are three opsin 5,related genes, designated cOpn5m (chicken opsin 5, mammalian type), cOpn5L1 (chicken opsin 5 - like 1), and cOpn5L2 (chicken opsin 5 - like 2), in the chicken genome. Quantitative PCR analysis has revealed that cOpn5m is the most abundant in the developing and early posthatching neural retina. In situ hybridization analysis has shown that cOpn5m is specifically expressed in subsets of differentiating ganglion cells and amacrine cells. These results suggest that the mammalian type opsin 5 may contribute to the development of these retinal cells in the chicken. Developmental Dynamics 237:1910,1922, 2008. © 2008 Wiley-Liss, Inc. [source] Arrested differentiation and epithelial cell degeneration in zebrafish lens mutantsDEVELOPMENTAL DYNAMICS, Issue 4 2001Thomas S. Vihtelic Abstract In a chemical mutagenesis screen, we identified two zebrafish mutants that possessed small pupils. Genetic complementation revealed these two lines are due to mutations in different genes. The phenotypes of the two mutants were characterized using histologic, immunohistochemical, and tissue transplantation techniques. The arrested lens (arl) mutant exhibits a small eye and pupil phenotype at 48 hr postfertilization (hpf) and lacks any histologically identifiable lens structures by 5 days postfertilization (dpf). In contrast, the disrupted lens (dsl) mutants are phenotypically normal until 5 dpf, and then undergo lens disorganization and cell degeneration that is apparent by 7 dpf. Histology reveals the arl mutant terminates lens cell differentiation by 48 hpf, whereas the dsl lens exhibits a defective lens epithelial cell population at 5 dpf. Lens transplantation experiments demonstrate both mutations are autonomous to the lens tissue. Immunohistochemistry reveals the retinal cells may suffer subtle effects, possibly due to the lens abnormalities. © 2001 Wiley-Liss, Inc. [source] Cytopathological diagnosis of adult retinoblastoma in a vitrectomy specimen,DIAGNOSTIC CYTOPATHOLOGY, Issue 1 2010Maria E. Orellana M.D. Abstract Retinoblastoma (RB) is extremely rare in adults. We describe a case of RB diagnosed by cytology in a vitrectomy specimen of a 23-year-old patient who presented with diminished visual acuity and retinal detachment in the absence of a clinically-visible mass. Cytological examination of the vitreous fluid showed clusters of loosely cohesive atypical cells with high nuclear to cytoplasmic ratio and "salt and pepper" chromatin pattern in a background of normal neuronal retinal cells. Nuclear molding was present as well as numerous apoptotic bodies. The cells were focally positive for epithelial markers and showed strong and diffuse positivity for neuroendocrine markers. Ki-67 stained 90% of the "atypical cells" nuclei, in contrast to nonneoplastic retinal neuronal cells, which were negative for the marker. A diagnosis of RB was rendered, and subsequently was confirmed in the enucleation specimen. The cytological differential diagnosis is discussed as well as the role that cytology and immunohistochemistry can play in differentiating neoplastic cells from normal retinal cellular elements in vitreous fluid specimens. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source] A stress survival response in retinal cells mediated through inhibition of the serine,/,threonine phosphatase PP2AEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2010Sorcha Finnegan Abstract Cell survival signalling involving the PI3K/Akt survival pathway can be negatively regulated by several phosphatases including PP2A. When retinal-derived 661W cells were subjected to trophic factor deprivation this initiated a survival response through inhibition of the activity of PP2A and subsequent upregulation of the Erk and Akt survival pathways. We show this survival response via inhibition of PP2A activity was due in part to increased reactive oxygen species production when retinal cells were deprived of trophic factors. Inhibition of PP2A activity was mediated by a rapid and transient increase in phosphorylation at Tyr307, accompanied by an increase in demethylation and a decrease in the methylated form. Pre-treatment with N -acetyl- l -cysteine, which is involved in scavenging reactive oxygen species, prevented PP2A inhibition and subsequent upregulation of survival pathways. Pre-treatment with the Src family kinase inhibitor PP2 resulted in approximately 50% reduction in cellular levels of phospho-PP2A in trophic factor-deprived 661W cells, suggesting an Src tyrosine kinase had a role to play in this redox regulation of cell survival. We observed similar events in the rd10 mouse retina where there was an increased survival response prior to retinal cell death mediated through an increase in both phospho-PP2A and phospho-Gsk. Together, these results demonstrate that when retinal cells are stressed there is an initial struggle to survive, mediated through inhibition of PP2A and subsequent upregulation of survival pathways, and that these events occur simultaneously with production of reactive oxygen species, thus suggesting an important cell-signalling role for reactive oxygen species. [source] Differentiation-dependent sensitivity to cell death induced in the developing retina by inhibitors of the ubiquitin-proteasome proteolytic pathwayEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2001D. D. C. Neves Abstract The effects of inhibitors of proteasome function were studied in the retina of developing rats. Explants from the retina of neonatal rats at postnatal day (P) 3 or P6 were incubated with various combinations of the proteasome inhibitor carbobenzoxyl-leucinyl-leucinyl-leucinal (MG132), the protein synthesis inhibitor anisomycin, or the adenylyl cyclase activator forskolin. MG132 induced cell death in a subset of cells within the neuroblastic (proliferative) layer of the retinal tissue. The cells sensitive to degeneration induced by either MG132 or anisomycin, were birthdated by bromodeoxyuridine injections. This showed that the MG132-sensitive population includes both proliferating cells most likely in their last round of cell division, and postmitotic undifferentiated cells, at a slightly earlier stage than the population, sensitive to anisomycin-induced cell death. The results show that sensitivity to cell death induced by proteasome inhibitors defines a window of development in the transition from the cell cycle to the differentiated state in retinal cells. [source] Pigment epithelium-derived factor induces the production of chemokines by rat microgliaGLIA, Issue 4 2005Asako Takanohashi Abstract Many studies have shown that pigment epithelium-derived factor (PEDF) has neurotrophic effects on retinal cells and hippocampal, spinal cord, and cerebellar granule cell neurons, but much less work has examined the effects of PEDF on glia. In this study, we show that PEDF changes microglial morphology within 1 h of exposure, to a more deactivated form, while having no effect on the expression of such activation markers as OX-42 and ED-1. In contrast, urea activates acid phosphatase, and PEDF blocks that activation. PEDF also activates NF,B, accompanied by the induction of mRNAs and proteins for the chemokines macrophage inflammatory protein-1, (MIP-1,, MIP-2, and MIP-3,. All the chemokines stimulate acid phosphatase activity, and high doses of MIP-2 and MIP-3,), alter the morphology of the microglia at 1 h after treatment. These results suggest that the use of PEDF for clinical treatments, such as for retinal neovascularization, brain injury, or ischemia, should be undertaken with caution because of the possibility of induction of inflammation caused by microglial or other immune cell migration in response to the chemokines induced by PEDF. © 2005 Wiley-Liss, Inc. [source] Crosstalk between Hsp70 molecular chaperone, lysosomes and proteasomes in autophagy-mediated proteolysis in human retinal pigment epithelial cellsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009Tuomas Ryhänen Abstract The pathogenesis of age-related macular degeneration involves chronic oxidative stress, impaired degradation of membranous discs shed from photoreceptor outer segments and accumulation of lysosomal lipofuscin in retinal pigment epithelial (RPE) cells. It has been estimated that a major part of cellular proteolysis occurs in proteasomes, but the importance of proteasomes and the other proteolytic pathways including autophagy in RPE cells is poorly understood. Prior to proteolysis, heat shock proteins (Hsps), agents that function as molecular chaperones, attempt to refold misfolded proteins and thus prevent the accumulation of cytoplasmic protein aggregates. In the present study, the roles of the Hsp70 molecular chaperone and proteasomal and lysosomal proteolytic pathways were evaluated in human RPE cells (ARPE-19). The Hsp70 and ubiquitin protein levels and localization were analysed by Western blotting and immunofluorescense. Confocal and transmission electron microscopy were used to detect cellular organelles and to evaluate the morphological changes. Hsp70 levels were modulated using RNA interference and overexpression techniques. Cell viability was measured by colorimetric assay. The proteasome inhibitor MG-132 evoked the accumulation of perinuclear aggregates positive for Hsp70, ubiquitin-protein conjugates and the lysosomal membrane protein LAMP-2. Interestingly, the hsp70 mRNA depletion significantly increased cell death in conjunction with proteasome inhibition. We found that the accumulation of lysosomes was reversible: a cessation of proteasome inhibition led to clearance of the deposits via a mechanism believed to include autophagy. The molecular chaperone Hsp70, proteasomes and autophagy have an important regulatory role in the protein turnover of human RPE cells and may thus open new avenues for understanding degenerative processes in retinal cells. [source] Biochemical, histological and behavioural aspects of visual function during early development of rainbow troutJOURNAL OF FISH BIOLOGY, Issue 4 2004P. S. M. Carvalho Retinal structure and concentration of retinoids involved in phototransduction changed during early development of rainbow trout Oncorhynchus mykiss, correlating with improvements in visual function. A test chamber was used to evaluate the presence of optokinetic or optomotor responses and to assess the functionality of the integrated cellular, physiological and biochemical components of the visual system. The results indicated that in rainbow trout optomotor responses start at 10 days post-hatch, and demonstrated for the first time that increases in acuity, sensitivity to low light as well as in motion detection abilities occur from this stage until exogenous feeding starts. The structure of retinal cells such as cone ellipsoids increased in length as photopic visual acuity improved, and rod densities increased concurrently with improvements in scotopic thresholds (2·2 log10 units). An increase in the concentrations of the chromophore all-trans-retinal correlated with improvements of all behavioural measures of visual function during the same developmental phase. [source] Glutamate receptors modulate sodium-dependent and calcium-independent vitamin C bidirectional transport in cultured avian retinal cellsJOURNAL OF NEUROCHEMISTRY, Issue 2 2009Camila Cabral Portugal Abstract Vitamin C is transported in the brain by sodium vitamin C co-transporter 2 (SVCT-2) for ascorbate and glucose transporters for dehydroascorbate. Here we have studied the expression of SVCT-2 and the uptake and release of [14C] ascorbate in chick retinal cells. SVCT-2 immunoreactivity was detected in rat and chick retina, specially in amacrine cells and in cells in the ganglion cell layer. Accordingly, SVCT-2 was expressed in cultured retinal neurons, but not in glial cells. [14C] ascorbate uptake was saturable and inhibited by sulfinpyrazone or sodium-free medium, but not by treatments that inhibit dehydroascorbate transport. Glutamate-stimulated vitamin C release was not inhibited by the glutamate transport inhibitor l -,-threo-benzylaspartate, indicating that vitamin C release was not mediated by glutamate uptake. Also, ascorbate had no effect on [3H] d -aspartate release, ruling out a glutamate/ascorbate exchange mechanism. 2-Carboxy-3-carboxymethyl-4-isopropenylpyrrolidine (Kainate) or NMDA stimulated the release, effects blocked by their respective antagonists 6,7-initroquinoxaline-2,3-dione (DNQX) or (5R,2S)-(1)-5-methyl-10,11-dihydro-5H -dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801). However, DNQX, but not MK-801 or 2-amino-5-phosphonopentanoic acid (APV), blocked the stimulation by glutamate. Interestingly, DNQX prevented the stimulation by NMDA, suggesting that the effect of NMDA was mediated by glutamate release and stimulation of non-NMDA receptors. The effect of glutamate was neither dependent on external calcium nor inhibited by 1,2-bis (2-aminophenoxy) ethane-N,,N,,N,,N,,-tetraacetic acid tetrakis (acetoxy-methyl ester) (BAPTA-AM), an internal calcium chelator, but was inhibited by sulfinpyrazone or by the absence of sodium. In conclusion, retinal cells take up and release vitamin C, probably through SVCT-2, and the release can be stimulated by NMDA or non-NMDA glutamate receptors. [source] Post-transcriptional suppression of pathogenic prion protein expression in Drosophila neuronsJOURNAL OF NEUROCHEMISTRY, Issue 6 2003Nathan R. Deleault Abstract A wealth of evidence supports the view that conformational change of the prion protein, PrPC, into a pathogenic isoform, PrPSc, is the hallmark of sporadic, infectious, and inherited forms of prion disease. Although the central role played by PrPSc in the pathogenesis of prion disease is appreciated, the cellular mechanisms that recognize PrPSc and modulate its production, clearance, and neural toxicity have not been elucidated. To address these questions, we used a tissue-specific expression system to express wild-type and disease-associated PrP molecules heterologously in Drosophila melanogaster. Our results indicate that Drosophila brain possesses a specific and saturable mechanism that suppresses the accumulation of PG14, a disease-associated insertional PrP mutant. We also found that wild-type PrP molecules are maintained in a detergent-soluble conformation throughout life in Drosophila brain neurons, whereas they become detergent-insoluble in retinal cells as flies age. PG14 protein expression in Drosophila eye did not cause retinal pathology. Our work reveals the presence of mechanisms in neurons that specifically counterbalance the production of misfolded PrP conformations, and provides an opportunity to study these processes in a model organism amenable to genetic analysis. [source] Astaxanthin, a dietary carotenoid, protects retinal cells against oxidative stress in-vitro and in mice in-vivoJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2008Yoshimi Nakajima We have investigated whether astaxanthin exerted neuroprotective effects in retinal ganglion cells in-vitro and in-vivo. In-vitro, retinal damage was induced by 24-h hydrogen peroxide (H2O2) exposure or serum deprivation, and cell viability was measured using a WST assay. In cultured retinal ganglion cells (RGC-5, a rat ganglion cell-line transformed using E1A virus), astaxanthin inhibited the neurotoxicity induced by H2O2 or serum deprivation, and reduced the intracellular oxidation induced by various reactive oxygen species (ROS). Furthermore, astaxanthin decreased the radical generation induced by serum deprivation in RGC-5. In mice in-vivo, astaxanthin (100 mg kg,1, p.o., four times) reduced the retinal damage (a decrease in retinal ganglion cells and in thickness of inner plexiform layer) induced by intravitreal N -methyl- d -aspartate (NMDA) injection. Furthermore, astaxanthin reduced the expressions of 4-hydroxy-2-nonenal (4-HNE)-modified protein (indicator of lipid peroxidation) and 8-hydroxy-deoxyguanosine (8-OHdG; indicator of oxidative DNA damage). These findings indicated that astaxanthin had neuroprotective effects against retinal damage in-vitro and in-vivo, and that its protective effects may have been partly mediated via its antioxidant effects. [source] Induced pluripotent stem cells (iPSCs): the emergence of a new champion in stem cell technology-driven biomedical applicationsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 6 2010Anjan Kumar Das Abstract Pluripotent stem cells possess the unique property of differentiating into all other cell types of the human body. Further, the discovery of induced pluripotent stem cells (iPSCs) in 2006 has opened up new avenues in clinical medicine. In simple language, iPSCs are nothing but somatic cells reprogrammed genetically to exhibit pluripotent characteristics. This process utilizes retroviruses/lentiviruses/adenovirus/plasmids to incorporate candidate genes into somatic cells isolated from any part of the human body. It is also possible to develop disease-specific iPSCs which are most likely to revolutionize research in respect to the pathophysiology of most debilitating diseases, as these can be mimicked ex vivo in the laboratory. These models can also be used to study the safety and efficacy of known drugs or potential drug candidates for a particular diseased condition, limiting the need for animal studies and considerably reducing the time and money required to develop new drugs. Recently, functional neurons, cardiomyocytes, pancreatic islet cells, hepatocytes and retinal cells have been derived from human iPSCs, thus re-confirming the pluripotency and differentiation capacity of these cells. These findings further open up the possibility of using iPSCs in cell replacement therapy for various degenerative disorders. In this review we highlight the development of iPSCs by different methods, their biological characteristics and their prospective applications in regenerative medicine and drug screening. We further discuss some practical limitations pertaining to this technology and how they can be averted for the betterment of human life. Copyright © 2010 John Wiley & Sons, Ltd. [source] Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: A morphological and ERG studyTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2007Claudia Gargini Abstract Retinal degeneration 10 (rd10) mice are a model of autosomal recessive retinitis pigmentosa (RP), identified by Chang et al. in 2002 (Vision Res. 42:517,525). These mice carry a spontaneous mutation of the rod-phosphodiesterase (PDE) gene, leading to a rod degeneration that starts around P18. Later, cones are also lost. Because photoreceptor degeneration does not overlap with retinal development, and light responses can be recorded for about a month after birth, rd10 mice mimic typical human RP more closely than the well-known rd1 mutants. The aim of this study is to provide a comprehensive analysis of the morphology and function of the rd10 mouse retina during the period of maximum photoreceptor degeneration, thus contributing useful data for exploiting this novel model to study RP. We analyzed the morphology and survival of retinal cells in rd10 mice of various ages with quantitative immunocytochemistry and confocal microscopy; we also studied retinal function with the electroretinogram (ERG), recorded between P18 and P30. We found that photoreceptor death (peaking around P25) is accompanied and followed by dendritic retraction in bipolar and horizontal cells, which eventually undergo secondary degeneration. ERG reveals alterations in the physiology of the inner retina as early as P18 (before any obvious morphological change of inner neurons) and yet consistently with a reduced band amplification by bipolar cells. Thus, changes in the rd10 retina are very similar to what was previously found in rd1 mutants. However, an overall slower decay of retinal structure and function predicts that rd10 mice might become excellent models for rescue approaches. J. Comp. Neurol. 500:222,238, 2007. © 2006 Wiley-Liss, Inc. [source] Retinal and Optic Nerve DiseasesARTIFICIAL ORGANS, Issue 11 2003Eyal Margalit Abstract:, A variety of disease processes can affect the retina and/or the optic nerve, including vascular or ischemic disease, inflammatory or infectious disease, and degenerative disease. These disease processes may selectively damage certain parts of the retina or optic nerve, and the specific areas that are damaged may have implications for the design of potential therapeutic visual prosthetic devices. Outer retinal diseases include age-related macular degeneration, pathologic myopia, and retinitis pigmentosa. Although the retinal photoreceptors may be lost, the inner retina is relatively well-preserved in these diseases and may be a target for retinal prosthetic devices. Inner retinal diseases include retinal vascular diseases such as diabetic retinopathy, retinal venous occlusive disease, and retinopathy of prematurity. Other retinal diseases such as ocular infections (retinitis, endophthalmitis) may affect all retinal layers. Because the inner retinal cells, including the retinal ganglion cells, may be destroyed in these diseases (inner retinal or whole retinal), prosthetic devices that stimulate the inner retina may not be effective. Common optic nerve diseases include glaucoma, optic neuritis, and ischemic optic neuropathy. Because the ganglion cell nerve fibers themselves are damaged, visual prosthetics for these diseases will need to target more distal portions of the visual pathway, such as the visual cortex. Clearly, a sound understanding of retinal and optic nerve disease pathophysiology is critical for designing and choosing the optimal visual prosthetic device. [source] 2224: Oxygenation of the human retinaACTA OPHTHALMOLOGICA, Issue 2010E STEFANSSON Purpose Partial pressure of oxygen in the optic nerve and retina is regulated by the intraocular pressure and systemic blood pressure, the resistance in the blood vessels and oxygen consumption of the tissue. The PO2 is autoregulated and moderate changes in intraocular pressure, blood pressure or tissue oxygen consumption do not affect the retinal and optic nerve oxygen tension. Methods If the intraocular pressure is increased above 40 mmHg or the ocular perfusion pressure decreased below 50 mmHg the autoregulation is overwhelmed and the optic nerve becomes hypoxic. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. Medical intervention can affect optic nerve PO2. Lowering the intraocular pressure tends to increase the optic nerve PO2, even though this effect may be masked by the autoregulation when the optic nerve PO2 and perfusion pressure is in the normal range. Results Carbonic anhydrase inhibitors increase retinal PO2 through a mechanism of vasodilatation and lowering of the intraocular pressure. Carbonic anhydrase inhibition reduces the removal of CO2 from the tissue and the CO2 accumulation induces vasodilatation resulting in increased blood flow and improved oxygen supply. This effect is inhibited by indomethacin but not other cyclo-oxygenase inhibitors. Conclusion Carbonic anhydrase inhibitors increase retinal blood flow and increase oxygen delivery. Glaucoma drugs and glaucoma surgery lower intraocular pressure, increase ocular perfusion pressure and blood flow. Demand of oxygen by retinal cells may be reduced through apoptosis and tissue atrophy, as well as active destruction of tissue by laser photocoagulation. [source] 2135: Influence of Hsp90 and HDAC inhibition and tubulin acetylation on perinuclear protein aggregation in human retinal pigment epithelial cellsACTA OPHTHALMOLOGICA, Issue 2010K KAARNIRANTA Purpose Retinal pigment epithelial (RPE) cells are continually exposed to oxidative stress that contributes to protein misfolding, aggregation and functional abnormalities during aging. The protein aggregates formed at the cell periphery are delivered along the microtubulus network by dynein dependent retrograde trafficking to a juxtanuclear location. Methods Cellular organelles were analysed by transmission electron microscopy of ARPE-19 cells exposed 5 µM MG-132, 0.25 µM geldanamycin (GA), 1 µM trichostatin A (TSA), 1 µM taxol (TAX) or 5 µM nocodazole (NOC) for 24 hours. In addition, the cells were treated simultaneously with GA or TSA or TAX or NOC and MG-132 up to 24 hours. Ubiquitin, Hsp90, Hsp70, acetylated tubulin and Hsc70 protein levels were analyzed by western blotting. Results Hsp90 inhibition by geldanamycin can effectively suppress proteasome inhibitor, MG-132 ,induced protein aggregation in a way that is an independent of HDAC inhibition, or the tubulin acetylation levels in ARPE-19 cells. However, the tubulin acetylation and polymerization state affects the localization of the proteasome-inhibitor ,induced aggregation. Conclusion Hsp90 inhibition is effectively related to regulation of protein aggregation that is independent of HDAC inhibition or tubulin acetylation levels in the RPE cells. Our findings open new perspectives for understanding the pathogenesis of protein aggregation in retinal cells and can be useful for the development of therapeutic treatments to prevent retinal cell deterioration. [source] Introduction on the multifaceted roles of nitric oxide in the retinaACTA OPHTHALMOLOGICA, Issue 2009NN OSBORNE Multifaceted roles of nitric oxide in the retina. N.N. Osborne. Nuffield Lab of Ophthalmology, University of Oxford, Oxford, United Kingdom Nitric oxide (NO), a free radical gas with a half-life of a few seconds is implicated in various physiological and pathophysiological roles associated with the retina and its vasculature. Generated by a family of nitric oxide synthetases (NOS), NO has been shown to bind to soluble guanylyl cyclase and to mitochondrial cytochrome c oxidase to activate defined signalling cascades. Different types of NOS exist and can be activated by calcium dependent (NOS1 and NOS3) or independent (NOS2) mechanisms. Generally, NOS1 is located to neurones while NOS2 and NOS3 are in glial and endothelial cells, respectively. NO is involved in communication between different neurones, glial cells and neurones, and in the interactions of endothelial cells with pericytes and neurones. As a consequence, a reduction in the generation of endogenous NO in the healthy retina can result in vasoconstriction; the consequences of such an affect on the retina and alterations in visual processing may alter the photoreceptor transduction mechanism and communication between retinal cells. The binding of NO to mitochondrial cytochrome c oxidase to effectively compete with oxygen has been suggested be involved in a number of processes. NO-elicited events act as triggers by which mitochondrial signal transduction cascades become involved in the induction of cellular defence mechanisms and adaptive responses. Moreover, the effect of NO on the electron transport chain might lead to mitochondrial dysfunction and pathology. NO clearly has a multifaceted role in the healthy and unhealthy retina. [source] Protein screening in vitreous samples of patients with retinal vein occlusionACTA OPHTHALMOLOGICA, Issue 2009HT AGOSTINI Purpose The aim of the study was to identify proteins involved in the pathogenesis of retinopathy after retinal vein occlusion. In retinal vein occlusion, proteins penetrate from leaky vessels into the vitreous. Alternatively, retinal cells produce protein factors and release them into the vitreous. Methods Vitreous and plasma samples of patients with retinal vein occlusion or macular pucker / macular hole were analyzed by antibody microarrays and ELISA. Results An antibody based microarray with more than 500 target for screening vitreous samples initially was less enlightening than antibody arrays providing the possibility to quantify up to 30 proteins in an ELISA-like microassay. Standard curves of antibody microarrays are as linear as those of ELISAs. VEGF values were similar to values measured by ELISA. Conclusion In our screen, we found some candidate factors which are currently investigated for their potential of influencing retinopathy after retinal vein occlusion. The use of microarrays to identify protein factors involved in retinal disease in the vitreous will be discussed. [source] What is the consequence of retinal detachment on anatomy and function?ACTA OPHTHALMOLOGICA, Issue 2009C CREUZOT Purpose To present the structural and functional consequences on retina after retinal detachment Methods Author will show the consequences of experimental retinal detachment in animal models. These changes prevent retinal cells from a normal post-operative functioning. However, these conditions have to be differentiated from post-operative visual loss due to macular edema, long-standing subretinal fluid, epiretinal membrane or macular hole formation. Results Retinal detachment leads to severe changes on retinal cells: outer segment shortening, fibrosis, glial proliferation. This situation is the target of neuroprotective treatment. By contrast, some situations where the bad recevoery is due to an associated disease (edema, membrane...) illustrated by clinical cases can need surgical treatment. Conclusion Bad functional recovery after retinal detachment can be explained by anatomic consequences on photoreceptors with subclinical fibrosis or some associated complications. [source] New insights into the pathogenic role of advanced glycation in diabetic retinopathyACTA OPHTHALMOLOGICA, Issue 2008AW STITT Purpose Retinopathy is the most common microvascular complication of diabetes. The clinicopathology of microvascular lesions and neuroglial dysfunction in the diabetic retina have been extensively studied, although the relative contribution of various biochemical sequelae of hyperglycaemia remains ill-defined. The formation and accumulation of advanced glycation endproducts (AGEs) is an important pathogenic pathway in the progression of diabetic retinopathy although some of the cellular and molecular pathologies initiated by these adducts in retinal cells remain unknown. Methods This presentation will cover several aspects of AGE-linked retinal pathology and demonstrate opportunities for therapeutic intervention. The studies outlined will cover a wide range of molecular cell biology approaches using appropriate in vitro and in vivo model systems. Results It will be demonstrated that AGEs form in vivo in the diabetic retina through the reaction of alpha-oxaloaldehydes leading to significant modifications of retinal proteins. Evidence will be presented to demonstrate that these AGEs act as significant effectors of retinal vascular and neuroglial cell dysfunction, leading to pro-inflammatory responses, growth factor imbalance and, ultimately, neurovascular lesions such as blood retinal barrier dysfunction and microvascular degeneration. The protective role of novel AGE-inhibitors will also be shown. Conclusion Evidence now points towards a pathogenic role for advanced glycation in the initiation and progression of diabetic retinopathy and this review lecture will outline the current state of knowledge of AGE-related pathology in the retina at a cellular and molecular level. [source] | |||||||||||||