Toward the realization of a better aged society: messages from gerontology and geriatrics.

Unlabelled: 1.

Background: Recent medical advancements, and improvements in hygiene and food supply have led to Japan having the longest life expectancy in the world. Over the past 50 years, the percentage of the elderly population has increased fourfold from 5.

[Pilot study to resolve problems of visual acuity assessment in grading vision of the physically handicapped--visual acuity and difficulties in daily life of age-related macular degeneration-].

Purpose: To resolve the problems of visual acuity assessment in grading the vision of the physically handicapped as proposed by the Subcommittee for Promoting the Realization of a Cohesive Society with the Visually Disabled, Science Council of Japan, a method suitable for assessing visual disturbances, and the relationship between the degree of visual disturbances and the degree of difficulty in activities of daily life are clarified.

Subjects And Methods: 151 persons with age-related macular degeneration were studied. Examination methods for measuring visual acuity and reading performance were studied, and interviews using the daily living task dependent on vision (DLTV) questionnaire were performed.

Molecular properties of rhodopsin and rod function.

Signal transduction in rod cells begins with photon absorption by rhodopsin and leads to the generation of an electrical response. The response profile is determined by the molecular properties of the phototransduction components. To examine how the molecular properties of rhodopsin correlate with the rod-response profile, we have generated a knock-in mouse with rhodopsin replaced by its E122Q mutant, which exhibits properties different from those of wild-type (WT) rhodopsin.

Cyclic stretch-induced reactive oxygen species generation enhances apoptosis in retinal pericytes through c-jun NH2-terminal kinase activation.

Hypertension is known to exacerbate diabetic complications, such as retinopathy and nephropathy. Apoptosis of retinal vascular pericytes has been well established as the earliest conceivable change in diabetic retinopathy. In this study, we investigated the contribution of cyclic stretch, which mimics a hypertensive state to pericyte apoptosis.

EphrinA1 inhibits vascular endothelial growth factor-induced intracellular signaling and suppresses retinal neovascularization and blood-retinal barrier breakdown.

The Eph receptor/ephrin system is a recently discovered regulator of vascular development during embryogenesis. Activation of EphA2, one of the Eph receptors, reportedly suppresses cell proliferation and adhesion in a wide range of cell types, including vascular endothelial cells. Vascular endothelial growth factor (VEGF) plays a primary role in both pathological angiogenesis and abnormal vascular leakage in diabetic retinopathy.

Generation of knock-in mice carrying third cones with spectral sensitivity different from S and L cones.

Red-green color vision in primates is unique in the sense that it is mediated by two photoreceptor cells that are indistinguishable in all aspects except for their visual pigments. In order to generate an animal model for investigation of the interaction between red-green inputs at the molecular level, we applied knock-in technology and X-chromosome inactivation machinery to make a mouse model with cone cells possessing visual pigments with different spectral sensitivities. We introduced a S308A point mutation into the Green opsin gene allele on the X-chromosome.

Recovery of rod-mediated a-wave during light-adaptation in mGluR6-deficient mice.

The purpose of this study was to compare the a-waves of mGluR6-deficient mice (KO) to that of wild-type mice (WT), and to determine whether the light-adapted electroretinogram of the KO mice originate exclusively from cones. Dark-adapted a-waves were recorded under the same conditions from both types of mice. With a 96-cd/m(2) background, the a-wave from both types of mice showed a rapid recovery over a 50-min period.

Expression of connective tissue growth factor and its potential role in choroidal neovascularization.

Background: To determine the expression of connective tissue growth factor (CTGF) in choroidal neovascularization.

Methods: Surgically excised choroidal neovascular membranes (CNVMs) were obtained at vitrectomy from eight eyes with age-related macular degeneration, five eyes with high myopia, and two eyes with angioid streaks. Light microscopic immunohistochemical analysis was performed to detect CTGF, transforming growth factor beta 1 (TGF-beta1), vascular endothelial growth factor (VEGF), pancytokeratin, and smooth muscle actin (SMA).

Iris-derived cells from adult rodents and primates adopt photoreceptor-specific phenotypes.

Purpose: The purpose of this study was to investigate the effects of various genes related to photoreceptor development on rodent and primate iris cells and the potential of iris cells as donor cells for retinal transplantation.

Methods: Adult rat and monkey iris tissue were cultured in serum-free medium containing basic fibroblast growth factor. Gene deliveries of Crx, Nrl, NeuroD and some combinations (Crx-Nrl, Crx-NeuroD) were performed with recombinant retrovirus.

Generation of Rx+/Pax6+ neural retinal precursors from embryonic stem cells.

We report directed differentiaion of retinal precursors in vitro from mouse ES cells. Six3+ rostral brain progenitors are generated by culturing ES cells under serum-free suspension conditions (SFEB culture) in the presence of Wnt and Nodal antagonists (Dkk1 and LeftyA), and subsequently steered to differentiate into Rx+ cells (16%) by treatment with activin and serum. Consistent with the characteristics of early neural retinal precursors, the induced Rx+ cells coexpress Pax6 and the mitotic marker Ki67, but not Nestin.

Angiopoietin-1 attenuates H2O2-induced SEK1/JNK phosphorylation through the phosphatidylinositol 3-kinase/Akt pathway in vascular endothelial cells.

Oxidative stress activates various signal transduction pathways, including Jun N-terminal kinase (JNK) and its substrates, that induce apoptosis. We reported here the role of angiopoietin-1 (Ang1), which is a prosurvival factor in endothelial cells, during endothelial cell damage induced by oxidative stress. Hydrogen peroxide (H2O2) increased apoptosis of endothelial cells through JNK activation, whereas Ang1 inhibited H2O2-induced apoptosis and concomitant JNK phosphorylation.

Is removal of internal limiting membrane always necessary during stage 3 idiopathic macular hole surgery?

Purpose: To determine the indications for internal limiting membrane (ILM) removal in stage 3 idiopathic macular holes (MHs).

Methods: Focal posterior vitreous detachments (PVDs) at MH rims were examined preoperatively by optical coherence tomography and binocular slit-lamp fundus examination in 19 patients retrospectively. All eyes underwent pars plana vitrectomy and creation of a PVD, and some eyes underwent a second surgery to remove the ILM.

The role of estrogen and estrogen receptorbeta in choroidal neovascularization.

Purpose: Choroidal neovascularization (CNV) under the age of 50 is more often observed in women than in men. The effects of 17beta-estradiol (E2) on choroidal neovascularization development were investigated both in animal models and cultured cells to see if estrogen receptors (ERs) are involved in the process.

Methods: CNV was induced by fundus laser photocoagulation in adult male and female rats.

In vivo three-dimensional evaluation of leukocyte behavior in retinal microcirculation of mice.

Purpose: To evaluate new physiologic and three-dimensional methods for monitoring leukocyte behavior in mouse retina.

Methods: Endotoxin-induced uveitis (EIU) was produced in mice by footpad injection of lipopolysaccharide (LPS). Leukocytes were labeled with acridine orange (AO).

Tlx, an orphan nuclear receptor, regulates cell numbers and astrocyte development in the developing retina.

Tlx belongs to a class of orphan nuclear receptors that underlies many aspects of neural development in the CNS. However, the fundamental roles played by Tlx in the control of eye developmental programs remain elusive. By using Tlx knock-out (KO) mice, we show here that Tlx is expressed by retinal progenitor cells in the neuroblastic layer during the period of retinal layer formation, and it is critical for controlling the generation of appropriate numbers of retinal progenies through the activities of cell cycle-related molecules, cyclin D1 and p27Kip1.

Alterations in expression of angiopoietins and the Tie-2 receptor in the retina of streptozotocin induced diabetic rats.

Purpose: The angiopoietin (Ang)/Tie-2 system may play a role in vascular integrity and angiogenesis. In this study, we investigated alterations of the gene expression of Ang-1 and Ang-2 in the retinas of streptozotocin (STZ) induced diabetic rats.

Methods: In situ hybridization, reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analyses were performed to determine the mRNA and protein content for Ang-1 and Ang-2 and the Tie2 receptor in the retinas of STZ diabetic and age matched control rats.

Potential for neural regeneration after neurotoxic injury in the adult mammalian retina.

It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N-methyl-D-aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells.

Pars plana vitrectomy for vitreous opacity associated with ocular sarcoidosis resistant to medical treatment.

Objective: To examine the results of pars plana vitrectomy for nonclearing vitreous opacities associated with ocular sarcoidosis that is resistant to corticosteroid treatment.

Methods: Eight consecutive patients (11 eyes) with vitreous opacities and uveitis associated with sarcoidosis were studied. All patients were resistant to or intolerant of corticosteroid therapy.

Drug delivery systems for vitreoretinal diseases.

The eye has an environment that is specific unto itself in terms of pharmacokinetics: the inner and outer blood-retinal barriers separate the retina and the vitreous from the systemic circulation and vitreous body, which physiologically has no cellular components, occupies the vitreous cavity, an inner space of the eye, and reduces practical convection of molecules. Considering this, development of a drug delivery system (DDS) is becoming increasingly important in the treatment of vitreoretinal diseases not only to facilitate drug efficacy but also to attenuate adverse effects. The DDS has three major goals: enhances drug permeation (e.

Analysis of choriocapillaris flow patterns by continuous laser-targeted angiography in monkeys.

Purpose: To investigate choriocapillaris flow patterns and its segmental distribution in monkeys by continuous laser-targeted angiography (LTA).

Methods: A slit lamp was modified to incorporate two kinds of lasers (argon and diode). Carboxyfluorescein (CF) was encapsulated in heat-sensitive liposomes and injected intravenously.

Transcription factor Ets-1 mediates ischemia- and vascular endothelial growth factor-dependent retinal neovascularization.

Transcription factor Ets-1 has been reported to regulate angiogenesis in vascular endothelial cells. Here, we investigated a mechanism that may regulate the expression of Ets-1 in vascular endothelial growth factor (VEGF)- and hypoxia-induced retinal neovascularization and that may have potential to inhibit ocular neovascular diseases. VEGF and hypoxia increased Ets-1 expression in cultured bovine retinal endothelial cells.

Simvastatin inhibits leukocyte accumulation and vascular permeability in the retinas of rats with streptozotocin-induced diabetes.

Leukocytes play important roles in the pathogenesis of diabetic retinopathy. Recently, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have been reported to exert various effects in addition to their lipid-lowering ability. We investigated the effects of simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, on leukocyte-induced diabetic changes in retinas.

Laser photocoagulation of indocyanine green angiographically identified feeder vessels to idiopathic polypoidal choroidal vasculopathy.

Purpose: To evaluate the efficacy of laser photocoagulation of indocyanine green angiographically identified feeder vessels to idiopathic polypoidal choroidal vasculopathic lesions.

Design: Interventional case series.

Methods: Fifteen eyes of 14 consecutive patients with idiopathic polypoidal choroidal vasculopathy lesions treated by laser photocoagulation of indocyanine green angiographically identified feeder vessels were investigated.