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 performed an expression analysis of pro- and anti-apoptotic mediators in the immature, post-natal day 6 (P6) and the post-mitotic adult P60 mouse retina. Laser capture microdissection (LCM) of the P6 and the P60 retina, followed by reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to elucidate changes in the mRNA expression of Apaf-1, caspase-3 and caspase-9 in the individual retinal layers in the young and mature tissue. RT-PCR and Western blotting of whole P6 and P60 retinal preparations was carried out to determine changes in other caspases and key survival mediators at the mRNA and protein level, respectively. Our results demonstrate that each neuronal cell layer in the adult retina down-regulates the gene expression of Apaf-1 and caspase-3, and to a lesser extent, caspase-9. The protein expression levels of other executioner and initiator caspases are also reduced in the adult tissue. Interestingly, XIAP, a potent caspase inhibitor, increases in expression in the adult retina. Additionally, we demonstrate age-dependent increased expression and activation status of the components of the MAPK transduction cascade. Conversely, we observe decreased PI3-K and AKT expression and decreased activity of AKT (pAKT) in the adult retina. Furthermore, results from RNAi experiments demonstrate an additional mechanism of PI3-K regulation in photoreceptor cells. Our findings suggest that a survival strategy adopted by the post-mitotic retina involves a down-regulation of key pro-apoptotic factors concomitant with changes in expression and activation status of certain pro-survival mediators.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
O'Driscoll C,Donovan M,Cotter TGdoi
10.1016/j.exer.2006.08.007subject
Has Abstractpub_date
2006-12-01 00:00:00pages
1482-92issue
6eissn
0014-4835issn
1096-0007pii
S0014-4835(06)00345-9journal_volume
83pub_type
杂志文章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 ...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2011.12.019
更新日期:2012-03-01 00:00:00
abstract::Reactive nitrogen species, in particular, peroxynitrite (ONOO(-)) have been proposed to play an important role in the pathogenesis of endotoxin-induced uveitis (EIU). Tyrosine nitration by ONOO(-) has been shown in other model systems to inhibit the activity of the superoxide anion quenching enyzme, manganese superoxi...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.2002.1141
更新日期:2002-04-01 00:00:00
abstract::Obesity has been associated with abnormal lipid metabolism and with tissue hypoxia. Human Bruch's membrane (BrM) lipid deposits have been proposed to create a diffusion barrier to metabolic exchange between the choroid and photoreceptors, delaying the regeneration of photopigments. The speed of retinal dark adaptation...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2019.02.007
更新日期:2019-04-01 00:00:00
abstract::The present study was designed to identify genomic loci modulating the susceptibility of retinal ganglion cells (RGC) to elevated intraocular pressure (IOP) in the BXD recombinant inbred mouse strain set. IOP was elevated by injecting magnetic microspheres into the anterior chamber and blocking the trabecular meshwork...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2017.12.013
更新日期:2018-04-01 00:00:00
abstract::Murine macrophages treated with TGF-beta2 are capable of inducing anterior chamber-associated immune deviation (ACAID), and these macrophages are characterized by impaired IL-12 production and CD40 expression, consequently failing to promote Th1 cell differentiation. In this study, we investigated whether human monocy...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2006.05.005
更新日期:2006-10-01 00:00:00
abstract::Tenon's fibroblast (TF) bleb encapsulation is a common cause of filtering surgery failure. Various pharmacologic agents have been used in an attempt to inhibit this response. The effects of three angiogenesis inhibitors were studied. AGM-1470, a fumagillin analog and hydrocortisone 21-phosphate (HC21P) complexed with ...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.1994.1037
更新日期:1994-04-01 00:00:00
abstract::Post-translational modifications and/or structural changes induced by modifications are likely causes of the decrease in crystallin solubility associated with aging and the development of cataract. Characterization of human lens crystallins by mass spectrometry has demonstrated that betaB2-crystallin undergoes less mo...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.2001.1023
更新日期:2001-08-01 00:00:00
abstract::AII amacrine cells are critical interneurons in the rod pathway of mammalian retina, active primarily in dim lighting conditions. Melatonin, a neuromodulator produced at night in the retina, is believed to induce retinal adaptation to dim lighting conditions in most vertebrate species examined to date, including human...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/s0014-4835(03)00123-4
更新日期:2003-09-01 00:00:00
abstract::To facilitate the peeling of internal limiting membrane or epiretinal membrane in vitreoretinal surgery, trypan blue (TB) and indocyanine green (ICG) have been used. However, the cytotoxicity of these dyes have been concerned. The aim of this study was to investigate the neurotoxic effects of TB on rat retinal ganglio...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2005.02.010
更新日期:2005-10-01 00:00:00
abstract::As wounds in stratified epithelia close, the numbers of cells at the leading edge of migration decreases. It is not known whether cells at the leading edge are continually replaced or whether some retain their position at the leading edge over time. Replication-deficient adenovirus carrying the green fluorescent prote...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.2001.1115
更新日期:2002-02-01 00:00:00
abstract::Cochlin deposits were observed in the trabecular meshwork (TM) of 8-month-old glaucomatous DBA/2J mice, coincident with the reported onset of increased intraocular pressure and optic nerve damage. An age-dependent increase in cochlin was observed up to 10 months of age and was paralleled by a decrease in type II colla...
journal_title:Experimental eye research
pub_type: 信件
doi:10.1016/j.exer.2005.01.028
更新日期:2005-05-01 00:00:00
abstract::Selective pericyte loss, the histological hallmark of early diabetic retinopathy (DR), enhances the breakdown of the blood-retinal barrier (BRB) in diabetes. However, the role of pericytes on BRB alteration in diabetes and the signaling pathways involved in their effects are currently unknown. To understand the role o...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2020.108043
更新日期:2020-06-01 00:00:00
abstract::Keratoconus is a debilitating corneal thinning disease that principally develops in the second and third decades of life. Our group previously developed a novel approach to studying keratoconus, based on the observation that there is a gradient of damage across the keratoconic cone. We identified a number of cellular ...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/s0014-4835(03)00148-9
更新日期:2003-10-01 00:00:00
abstract::Cynomolgus (Macaca fascicularis) monkeys from three families, which showed symptoms of early onset macular degeneration was studied. Two proteins, albumin and glyceraldehyde 3-phosphate dehydrogenase, were found to have markedly altered concentrations in whole retina of the monkeys with early onset macular degeneratio...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.1996.0026
更新日期:1996-03-01 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::The localization of [35S]-sulfate and [3H]-glucosamine in the hamster non-pigmented ciliary epithelium was studied by light and electron microscopic autoradiography. The radioactivity was concentrated in the Golgi complex of the non-pigmented ciliary epithelium 10 mins after injections of [35S]-sulfate or [3H]-glucosa...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(83)90009-x
更新日期:1983-02-01 00:00:00
abstract::Oxidative stress and inflammation are important pathological mechanisms in many neurodegenerative diseases, including age-related macular degeneration (AMD). The very low-density lipoprotein receptor knockout mouse (Vldlr-/-) has been identified as a model for AMD and in particular for retinal angiomatous proliferatio...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2013.08.003
更新日期:2013-11-01 00:00:00
abstract::The elimination of spermine, the end product of cellular polyamine, from the retina to the blood across the blood-retinal barrier (BRB) was investigated. The in vivo microdialysis study revealed that the elimination of [(3)H]spermine from vitreous humor after vitreous bolus injection was in a biexponential manner. The...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2014.05.002
更新日期:2014-07-01 00:00:00
abstract::In this study, we examined calcium-mediated degradation of a neurofilament protein (NFP), and autolytic activation of calpain in Lewis rat optic nerve in vitro. After incubation with calcium, homogenized optic nerve samples were analysed by SDS-PAGE in association with ECL immunoblot techniques. 68 kD NFP, calpain, an...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.1997.0286
更新日期:1997-07-01 00:00:00
abstract::When aqueous humour outflow resistance is measured by two-level constant pressure perfusion in non-human primate eyes, a progressive decrease in outflow resistance, known as the 'washout effect' occurs with time. The effect of age on total outflow resistance washout (the reciprocal of outflow facility (OF)) was determ...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2005.04.010
更新日期:2005-12-01 00:00:00
abstract::Our previous gene expression analysis suggested that conjunctival epithelial cells of Sjögren's syndrome (SS) are inclined to hyper-proliferation and keratinisation status. The goal of this study is to elucidate whether such pathological situations really exist in the conjunctival epithelium of SS. Also, involvement o...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2005.07.009
更新日期:2006-03-01 00:00:00
abstract::Tissue from the outflow system of six surgically enucleated aged eyes was used for an ultrastructural immunocytochemical study of the distribution of laminin and type IV collagen. The immunogold technique provided precise localization of laminin beneath lining endothelial cells of the inner wall of Schlemm's canal. La...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(90)90054-x
更新日期:1990-12-01 00:00:00
abstract::Myopia is one of the leading ocular disorders causing visual impairment worldwide, with the prevalence increasing rapidly. It's a significant global public health concern in 21st century. Myopia, particularly high myopia, often exhibits apparent familial aggregation, and multiple evidences have shown that genetic fact...
journal_title:Experimental eye research
pub_type: 杂志文章,评审
doi:10.1016/j.exer.2019.107778
更新日期:2019-11-01 00:00:00
abstract::Na,K-ATPase was detected in crude microsomes of guinea-pig retinal layers, cornea and lens by immunoblotting using antibodies generated against purified kidney Na,K-ATPase. The antiserum cross-reacted with the alpha catalytic subunit of the enzyme from the eye tissues but not the beta glycoprotein subunit, suggesting ...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(85)90136-8
更新日期:1985-05-01 00:00:00
abstract::The chelating agent Na2EDTA was perfused through the anterior chambers of monkeys eyes in an attempt to find a concentration that would cause a rise in outflow facility without harming the cornea or anterior uvea. Na2EDTA (0.5 mM) proved effective in increasing the facility within 60 min. There were marked effects on ...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/s0014-4835(87)80002-7
更新日期:1987-02-01 00:00:00
abstract::Experimental autoimmune uveoretinitis (EAU) in mice provides a useful platform to study the pathogenesis and experimental therapeutics of human uveitis. One often used EAU model employs C57BL/6 (B6) mice sensitized with a peptide residue having 1 to 20 amino acids of human interphotoreceptor retinoid binding protein (...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2020.108406
更新日期:2020-12-19 00:00:00
abstract::The effect of acute exposure to various intensities of white light on visual behavior and retinal structure was evaluated in the T4R RHO dog, a naturally-occurring model of autosomal dominant retinitis pigmentosa due to a mutation in the Rhodopsin gene. A total of 14 dogs (ages: 4-5.5 months) were used in this study: ...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2016.04.006
更新日期:2016-05-01 00:00:00
abstract::We examined the role of Müller (glial) cells in buffering light-evoked changes in extracellular K+ concentration, [K+]o, in the isolated retina of the toad, Bufo marinus. We found evidence for two opposing Müller cell current loops that are generated by a light-evoked increase in [K+]o in the inner plexiform layer. Th...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/s0014-4835(05)80166-6
更新日期:1992-10-01 00:00:00
abstract::Corneal endothelium appears to be an important target tissue for retinoids and epidermal growth factor (EGF). We report here that retinoic acid, or its synthetic analogue CBS-211 A (10(-8)-10(-7) M) dose-dependently enhances the mitogenic effect of EGF on cultured bovine corneal endothelial cells (BCEC). Furthermore, ...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(90)90169-u
更新日期:1990-07-01 00:00:00
abstract::Following the identification of potent, orally active inhibitors of aldose reductase, the next challenge comes in demonstrating clinical utility in the treatment of diabetic complications. It is not feasible to conduct pivotal studies in all indications within the same trial and neuropathy evolved as the lead indicati...
journal_title:Experimental eye research
pub_type: 临床试验,杂志文章,评审
doi:10.1016/0014-4835(90)90103-2
更新日期:1990-06-01 00:00:00