Abstract：
:RPE65-related Leber's congenital amaurosis (LCA) is a rod-cone dystrophy whose clinical outcome is mainly attributed to the loss of rod photoreceptors followed by cone degeneration. Pathogenesis in Rpe65(-/-) mice is characterized by a slow and progressive degeneration of rods dependent on the constitutive activation of unliganded opsin. We previously reported that this opsin-mediated apoptosis of rods was dependent on Bcl-2-apoptotic pathway and Bax-induced pro-death activity. In this study, we report early initial apoptosis in the newly differentiated retina of Rpe65(-/-) mice. Apoptotic photoreceptors were identified as rods and resulted from pathological phototransduction signaling. This wave of early apoptosis triggered Bcl-2-related pathway and Bax apoptotic activity, while activation of the caspases was not induced. Following cellular stress, multiple signaling pathways are initiated which either commit cells to death or trigger pro-survival responses including autophagy. We report that Bcl-2-related early rod apoptosis was associated with the upregulation of autophagy markers including chaperone-mediated autophagy (CMA) substrate receptor LAMP-2 and lysosomal hydrolases Cathepsin S and Lysozyme. This suggests that lysosomal-mediated autophagy may be triggered in response to early rod apoptosis in Rpe65-LCA disease. These results highlight that Rpe65-related primary stress induces early signaling events, which trigger Bax-induced-apoptotic pathway and autophagy-mediated cellular response. These events may determine retinal cell fate, progression and severity of the disease.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Métrailler S,Schorderet DF,Cottet Sdoi
10.1016/j.exer.2011.12.019subject
Has Abstractpub_date
2012-03-01 00:00:00pages
70-81issue
1eissn
0014-4835issn
1096-0007pii
S0014-4835(11)00416-7journal_volume
96pub_type
杂志文章abstract：:Type I and type II isoenzymes of cyclic AMP-dependent protein kinase were identified by anion exchange chromatography and immunoblotting in human retina at various stages of development. The type I form was typical of the early fetal stage during which proliferation and migration were the primary cellular processes. I...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(89)90059-6
更新日期：1989-06-01 00:00:00
abstract：:Photoreceptor degeneration in human photoreceptor dystrophies and in the relevant animal models has been thought to be executed by one common mechanism -- caspase-mediated apoptosis. However, recent experiments have challenged this concept. In previous experiments, analyzing gene expression in the degenerating rd/rd m...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2006.01.014
更新日期：2006-08-01 00:00:00
abstract：:The presence of the alpha(1)-adrenoceptor subtypes in various parts of the pig and rabbit eyes was investigated using [(3)H]-prazosin radioligand binding. The characterization of the subtypes was achieved by performing competition experiments with various subtype selective drugs. In the pig retina, both alpha(1A)- and...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1999.0753
更新日期：2000-01-01 00:00:00
abstract：:A simple culture method that was recently developed in our laboratory was applied to the chick iris tissues to characterize neural stem/progenitor-like cells. Iris tissue is a non-neuronal tissue and does not contain any neuronal cells. In the present study we isolated iris tissues from chick embryos just prior to hat...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2014.04.007
更新日期：2014-06-01 00:00:00
abstract：:The purpose of our study was to establish a system for culturing normal human conjunctival epithelial (NHCE) cells under serum-free culture conditions without compromising their ability to differentiate into a mucous epithelium. To this end, small pieces of normal conjunctiva were biopsied from patients undergoing cat...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2007.04.005
更新日期：2007-08-01 00:00:00
abstract：:Retinal degenerations, regardless of the initiating event or gene defect, often result in a loss of photoreceptors. This formal deafferentation of the neural retina eliminates the intrinsic glutamatergic drive of the sensory retina and, perhaps more importantly, removes coordinated Ca++-coupled signaling to the neural...
journal_title：Experimental eye research
pub_type： 杂志文章,评审
doi：10.1016/j.exer.2005.03.006
更新日期：2005-08-01 00:00:00
abstract：:Herpes simplex virus type-1 (HSV-1) infection leads to impaired corneal sensation and, in severe cases, to corneal ulceration, melting and perforation. Here, we explore the potential therapeutic action of pigment epithelial-derived factor (PEDF) plus docosahexaenoic acid (DHA) on corneal inflammation and nerve regener...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2017.06.015
更新日期：2017-08-01 00:00:00
abstract：:Vitreous from bovine, human and chick embryo has been found to contain a trypsin inhibitory activity. Chymotrypsin-inhibitory activity was also identified in bovine and chick embryo vitreous. Following either ultrafiltration or Bio Gel P-10 chromatography, these activities appear in fractions having a molecular weight...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(85)90031-4
更新日期：1985-11-01 00:00:00
abstract：:The CLN2 form of neuronal ceroid lipofuscinosis is an autosomal recessively inherited lysosomal storage disease that is characterized by progressive vision loss culminating in blindness, cognitive and motor decline, neurodegeneration, and premature death. CLN2 disease results from mutations in the gene that encodes th...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2015.02.012
更新日期：2015-05-01 00:00:00
abstract：:A dark reaction is known to occur in retinal extracts of the gecko (Gekko gekko), in which the natural 11-cis-chromophore of the 521-pigment is apparently replaced by adding 9-cis-retinal to form the 9-cis-photopigment. With chloride-deficient extracts the reaction involves some 70% of the 521-pigment. Anions like nit...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(89)90074-2
更新日期：1989-07-01 00:00:00
abstract：:Müller cells can completely repair retinal injury by acting as endogenous stem/progenitor cells in lower-order vertebrates. However, a safe and effective approach to activate progenitor potential of retinal Müller cells in higher-order vertebrates, which rarely re-enter the cell cycle, is a bottleneck problem. In the ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2015.01.008
更新日期：2015-03-01 00:00:00
abstract：:The ocular lens is surrounded by the lens capsule, which is an elastic and unusually thick basal membrane. Anionic sites are thought to be responsible for charge-selective permeability barriers in basal membranes. We have used cationic colloidal gold as a tracer for anionic binding sites to investigate the distributio...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.2000.0952
更新日期：2001-03-01 00:00:00
abstract：:Jin H. Kinoshita has had a major role in fostering investigations on the molecular biology of the eye during his tenure as Scientific Director of the National Eye Institute (N.E.I.). His appreciation and support of molecular biology have been the basis for many advances in this area in the N.E.I. and have led to a fer...
journal_title：Experimental eye research
pub_type： 杂志文章,评审
doi：10.1016/0014-4835(90)90121-a
更新日期：1990-06-01 00:00:00
abstract：:The purpose of this study was to evaluate the inhibitory activity of the heparan sulfate suleparoide on vascular cell growth in vitro and angiogenesis in vivo. Human HUV-EC-C endothelial cell proliferation and microvessel sprouting from cultured rat aortic rings were assayed by the bioreduction of 3-[4,5-dimethylthiaz...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1998.0512
更新日期：1998-08-01 00:00:00
abstract：:Corneal endothelial wound healing following scrape injury in the rabbit and cat is characterized by cell spreading and maintenance of a normal endothelial phenotype consisting of apically-localized, circumferential microfilament bands and cell border-associated ZO-1, a tight junction protein and marker for endothelial...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1996.0211
更新日期：1997-02-01 00:00:00
abstract：:The effects of the instillation of a PGE2-analogue (11-deoxy-13,14-didehydro-16 (S)-methyl PGE2 methylester: FCE 20700) in the conjunctival sac of the rabbit were studied by means of two methods. The former is a clinical study (Dohlman test), the latter is a morphological investigation (semithin sections) on specimens...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(87)80113-6
更新日期：1987-11-01 00:00:00
abstract：:We have determined the pattern of RNA labeling (uridine incorporation) in the normal retina of the domestic cat. One eye in each of eight cats was labeled by injecting [3H]uridine into the vitreous cavity. Two of the labeled eyes had the lens and vitreous removed 10 days before labeling. Three additional animals recei...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(90)90066-4
更新日期：1990-08-01 00:00:00
abstract：:For in vivo mouse retinal imaging, especially with Adaptive Optics instruments, application of a contact lens is desirable, as it allows maintenance of cornea hydration and helps to prevent cataract formation during lengthy imaging sessions. However, since the refractive elements of the eye (cornea and lens) serve as ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2018.03.027
更新日期：2018-07-01 00:00:00
abstract：:Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2014.09.004
更新日期：2014-11-01 00:00:00
abstract：:To assess the ability of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to detect blood retinal barrier (BRB) damage in patients with diabetic macular edema (DME). DCE-MRI with 0.1 mmol Gd-DTPA was used to measure BRB permeability in 10 healthy and visually normal subjects and eight patients with DME, ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2005.01.015
更新日期：2005-07-01 00:00:00
abstract：:Previous studies have relied on various electrodes or probes to monitor preretinal oxygen tension in an effort to gain insight into retinal oxygenation. In order to corroborate and extend the results of such studies, we developed a relatively non-invasive method of determining preretinal oxygen tension using 19F nucle...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(92)90099-e
更新日期：1992-07-01 00:00:00
abstract：:Prolyl oligopeptidase (EC 3.4.21.26) has been purified 26,000-fold from bovine lens tissue by anion-exchange chromatography, gel filtration and isoelectric focussing, with an overall yield of 11%. The purified enzyme exhibited an isoelectric point of 4.8, a pH optimum of 7.5 and a molecular mass of 72 kDa under both n...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1994.1086
更新日期：1994-07-01 00:00:00
abstract：:The effects of temperature on rod outer segment (ROS) length and membrane shedding were studied in a cyprinodont fish, Fundulus zebrinus. After 30 days in 14L/10D cyclic light and 17 degrees C, ROS length averaged 41.2 microns. Fish were then exposed to 7, 17 or 27 degrees C for 10 and 25 days before being sampled 5 h...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(05)80036-3
更新日期：1995-08-01 00:00:00
abstract：:The purpose of this study was to quantify how the elastic modulus of the ex vivo iris changes following stimulation by pilocarpine (PILO), phenylephrine (PE), and tropicamide (TROP). Irides (n = 20) were dissected from porcine eyes within 4 h post-mortem and tested uniaxially. Either the entire iris or sector thereof ...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2009.04.014
更新日期：2009-10-01 00:00:00
abstract：:Bubble-based acoustic radiation force aims to measure highly localized tissue viscoelastic properties. In the current investigation, acoustic radiation force was applied to laser-induced bubbles to measure age-related changes in the spatial distribution of elastic properties within in vitro porcine lenses. A potential...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2006.10.007
更新日期：2007-02-01 00:00:00
abstract：:Longitudinal (T1) magnetic relaxation times for the major phosphorus-containing metabolites present in the bovine and rabbit lens under organ culture conditions and in the bovine and rabbit globe have been determined. Significant differences in T1 for the major phosphorus metabolites in each case are observed, as well...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/0014-4835(84)90045-9
更新日期：1984-10-01 00:00:00
abstract：:Lens development and transparency have been hypothesized to depend on intercellular gap junction channels, consisting of alpha3 (Cx46) and alpha8 (Cx50) connexin subunits, to transport metabolites, secondary messages and ions between lens cells. To evaluate this hypothesis, we have generated alpha3(-/-) alpha8(-/-) do...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2006.03.013
更新日期：2006-09-01 00:00:00
abstract：:The aim of this study was to develop consistently focal elevated choroidal masses of human choroidal melanoma in immunosuppressed rabbits and to correlate the visualization of prognostically significant microcirculation patterns from confocal indocyanine green angiography with histologic microcirculation patterns. A h...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1998.0650
更新日期：1999-06-01 00:00:00
abstract：:Apoptosis, a cellular process critical to retinal neurogenesis, has been implicated in several neurodegenerative disorders. As the retina matures the suppression of apoptosis occurs and the emphasis shifts towards survival. To identify the cellular changes that bring about this critical shift in the balance, we perfor...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/j.exer.2006.08.007
更新日期：2006-12-01 00:00:00
abstract：:The aim of this study was to elucidate the expression of chemokines, their role and regulation in bacterial corneal infection using three bacterial strains (Pseudomonas. aeruginosa- invasive, cytotoxic and contact lens induced acute red eye strains) which have been shown to produce three distinct patterns of corneal d...
journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1016/s0014-4835(02)00270-1
更新日期：2003-02-01 00:00:00
