Health literacy has been associated with health-related knowledge and patient comprehension. This systematic review updates a 2004 review and found 96 eligible studies that suggest that low health ...

Low Health Literacy and Health Outcomes: An Updated Systematic Review

基礎講座 電気泳動(Electrophoresis)

Recent discoveries are redefining our view of cellular senescence as a trigger of tissue remodelling that acts during normal embryonic development and upon tissue damage. To achieve this, senescent cells arrest their own proliferation, recruit phagocytic immune cells and promote tissue renewal. This sequence of events - senescence, followed by clearance and then regeneration - may not be efficiently completed in aged tissues or in pathological contexts, thereby resulting in the accumulation of senescent cells. Increasing evidence indicates that both pro-senescent therapies and antisenescent therapies can be beneficial. In cancer and during active tissue repair, pro-senescent therapies contribute to minimize the damage by limiting proliferation and fibrosis, respectively. Conversely, antisenescent therapies may help to eliminate accumulated senescent cells and to recover tissue function.

Cellular senescence: from physiology to pathology.

Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy.

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Cellular senescence in aging and age-related disease: from mechanisms to therapy

Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood–retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases.

Ocular Drug Delivery

Purpose: Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by bone fragility. Ocular findings include blue sclera, low ocular rigidity, and thin corneal thickness. However, there are no documented cases linking OI and primary open angle glaucoma (POAG). In this report, we describe three individuals, one isolated case and two from a multiplex family, with OI type I and POAG. Methods: Available family members with OI and POAG had a complete eye examination, including visual acuity, intraocular pressure (IOP), pachymetry, slit-lamp exam, dilated fundus exam, and visual fields. DNA from blood samples was sequenced and screened for mutations in COL1A1/2 and myocilin (MYOC). Results: All subjects had OI type I. Findings of POAG included elevated IOP, normal gonioscopy, and glaucomatous optic disc cupping and visual field loss. POAG cosegregated with OI in the multiplex family. The multiplex family had a single nucleotide insertion (c.540_541insC) in COL1A1 resulting in a frameshift mutation and a premature termination codon. The sporadic case had a COL1A1 splice acceptor site mutation (c.2452–2A>T or IVS36–2A>T) predicted to result in a premature termination codon due to intron inclusion or a cryptic splice site. None of the glaucoma cases had mutations or sequence changes in MYOC. Conclusions: We identified two novel mutations in COL1A1 in individuals with OI type I and POAG. Thus, some mutations in COL1A1 may be causative for OI and POAG. Alternatively, susceptibility genes may interact with mutations in COL1A1 to cause POAG.

/pdf/osteogenesis-imperfecta-and-primary-open-angle-glaucoma-4g8q88s269.pdf

Osteogenesis imperfecta and primary open angle glaucoma: Genotypic analysis of a new phenotypic association

Purpose To assess the effects of Rho-associated kinase (ROCK) inhibition on the intraocular penetration of timolol maleate. Methods Ex vivo porcine corneal penetration of timolol maleate, sotalol hydrochloride, or brinzolamide incubated with or without Y-27632 was determined in vertical Franz diffusion cells. The effect of ROCK inhibition on the vasodilation of porcine conjunctival vasculature was assessed by scanning electron microscopy (SEM) and immunohistochemical staining with subsequent laser-scanning confocal microscopy (LSCM). Experiments were conducted in New Zealand White (NZW) rabbits to assess the effect of ROCK inhibition on the intraocular distribution of timolol maleate. Results ROCK inhibition resulted in minimal alteration of ex vivo porcine corneal drug penetration of timolol, sotalol, or brinzolamide. SEM and LSCM experiments conducted with conjunctiva and sclera tissue in Franz diffusion cells suggested vasodilation in the conjunctival vasculature in the presence of Y-27632. Pretreatment of the eyes of NZW rabbits with Y-27632 resulted in aggregate fold reductions (1 hour, 0.25-fold; 4 hours, 0.45-fold) of timolol maleate drug concentrations in intraocular tissues (aqueous humor, lens, and iris) versus eyes not receiving Y-27632 pretreatment. Pretreatment with a vasoconstrictor, phenylephrine, resulted in a reversal of the effect of Y-27632 on diminished timolol maleate intraocular penetration in NZW rabbits. Conclusions ROCK inhibition reduced the intraocular penetration of administered timolol maleate presumably due to increased systemic elimination through the conjunctival vasculature. It is anticipated that care in order and timing of ROCK inhibitor administration will be warranted for those patients who may be on a multiple topical drug regimen for primary open-angle glaucoma.

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The effect of Rho-associated kinase inhibition on the ocular penetration of timolol maleate.

Background: Non-visual factors influence a person’s vision-related quality of life (VRQoL). The purpose of this study was to assess the relationship between health literacy and VRQoL in glaucoma patients. Methods: One hundred and ninety-five subjects with open-angle glaucoma participated in a cross-sectional patient survey and chart review. Subjects were administered a test of health literacy, an assessment of physical and mental well-being, and an assessment of VRQoL, the National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25). Charts were reviewed for visual acuity and visual field results. Results: In univariate analyses, older age (p Conclusions: Individuals with a lower health literacy do not appear to have a worse overall VRQoL compared with those with a higher literacy, but worse health literacy is associated with increased dependency.

https://bjo.bmj.com/content/bjophthalmol/92/6/779.full.pdf

Health literacy and vision-related quality of life

Cataract development has a strong relationship to increasing age in both humans and animals.1–4 There is considerable evidence to support the concept that oxidative stress and the generation of reactive oxygen species (ROS) can accelerate cataract development through damage to lens epithelial and fiber cells.5–8 Caloric restriction (CR) has been shown to induce alterations in both the endogenous generation of ROS and the activation of protective mechanisms against oxidative damage.9 CR has also been shown to delay cataract formation in both mice and rats3,9 and to extend the lifespan of several species.10–12 The specific mechanisms by which CR exerts such effects on cataract progression, oxidative stress, and lifespan are not completely understood. However, there is experimental evidence suggesting that some of the effects of CR are mediated by the silent information regulator (Sirt1) and downstream activation of several members of the Forkhead box O (FoxO) gene family.13

The FoxO genes encode a family of transcription factors that modulate the expression of genes involved in the cellular response to oxidative stress, DNA repair, and apoptosis.14 Activation of FoxO transcription factors can promote stress resistance by binding to the promoters of genes such as manganese superoxide dismutase and catalase.15,16 This gene family plays a central role in oxidative stress response and is an important mediator of hematopoietic stem cell resistance to physiologic oxidative stress.17

The naturally occurring polyphenol resveratrol (RES) is an activator of SIRT1 and the FoxO transcription factors and has been shown to mimic some of the effects of CR including decreased production of ROS and increased protection against oxidative stress. RES has been shown to suppress selenite-induced oxidative stress and cataract formation in rats18 and together with proanthocyanidin extract can reduce significantly ROS production in canine lens epithelial cells.19 Furthermore, the activation Jun-N-terminal kinase (JNK) plays an important role in cell death signaling.20 RES also inhibits H2O2-induced JNK phosphorylation in HLEB-3,21 which may be one mechanism to prevent cell death. Therefore, we choose also to analyze the effects of JNK inhibition in our model system. However, RES is known to have both pro- and anti-apoptotic effects that may be cell and context dependent. In other words, like many biological processes, the effects of a specific molecule can be different depending on the cellular background or environment. Currently, it is not known what factors may influence the disparate effects of RES on apoptosis. Here we evaluate the potential protective effects of RES under chronic oxidative stress conditions and investigate the role that FoxO transcription factors play on this molecule's effects in lens epithelial cells. We used both porcine and human primary lens epithelial cell cultures for our studies because of the limited availability of human tissue.

Resveratrol Prevention of Oxidative Stress Damage to Lens Epithelial Cell Cultures Is Mediated by Forkhead Box O Activity

Purpose: Coding variants in the optineurin gene (OPTN, GLC1E) have been reported to play a role in primary open-angle glaucoma (POAG) in various populations. This study investigated the role of OPTN sequence variants in patients with POAG in Ghana (West Africa). Methods: This is a case-control study of unrelated Ghanaian POAG cases and non-glaucomatous controls. Ascertainment criteria for POAG included the presence of glaucomatous optic nerve neuropathy, associated visual field loss, and elevated intraocular pressure (IOP) in both eyes, all in the absence of secondary causes of glaucoma. Controls had normal optic nerves, visual fields, and IOP. All the coding exons of OPTN were polymerase chain reaction (PCR) amplified and sequenced in all 140 cases and 130 controls using an ABI 3730 DNA analyzer. Results: All the coding exons of OPTN were sequenced in 140 POAG patients and 130 controls. Several coding variants were identified including M98K, A134A, V147L, P292P, A301G, S321S, and E322K. Three coding variants (V147L, P292P, and A301G) have not been reported previously. There were no significant differences on the frequencies of all the identified variants between POAG cases and controls in this population. Conclusions: This is the first comprehensive study of OPTN in a single West African population. Our results suggest that coding variants in OPTN may not contribute to the risk for POAG in persons of West African descent. Glaucoma is a group of disorders defined by a

/pdf/optineurin-coding-variants-in-ghanaian-patients-with-primary-24gwe5ur82.pdf

Pratap Challa

Papers

Osteogenesis imperfecta and primary open angle glaucoma: Genotypic analysis of a new phenotypic association

The effect of Rho-associated kinase inhibition on the ocular penetration of timolol maleate.

Health literacy and vision-related quality of life

Resveratrol Prevention of Oxidative Stress Damage to Lens Epithelial Cell Cultures Is Mediated by Forkhead Box O Activity

Optineurin coding variants in Ghanaian patients with primary open-angle glaucoma.