Evidence map›Paper›PMID 24107965›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013

Klotho regulates retinal pigment epithelial functions and protects against oxidative stress.

Maria Kokkinaki, Mones Abu-Asab, Nishantha Gunawardena, Gerard Ahern, Monica Javidnia, John Young, Nady Golestaneh

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 1 country.

Maria KokkinakiDepartments of Ophthalmology, Pharmacology and Physiology, Neurology, and Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, Department of Anatomy, Howard University College of Medicine, Washington, DC 20059, and National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.
Mones Abu-Asab
Nishantha Gunawardena
Gerard Ahern
Monica Javidnia
John Young
Nady Golestaneh
Georgetown University · USGeorgetown University Medical Center · USHoward University · USNational Institutes of Health · USOphthalmology Associates (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The retinal pigment epithelium (RPE) is a highly specialized CNS tissue that plays crucial roles in retinal homeostasis. Age-related morphological changes in the RPE have been associated with retinal degenerative disorders; our understanding of the underlying molecular mechanisms, however, remains incomplete. Here we report on a key role of Klotho (Kl), an aging-suppressor gene, in retinal health and RPE physiology. Kl(-/-) mice show RPE and photoreceptor degeneration, reduced pigment synthesis in the RPE, and impaired phagocytosis of the outer segment of the photoreceptors. Klotho protein (KL) is expressed in primary cultured human RPE, and regulates pigment synthesis by increasing the expression of MITF (microphthalmia transcription factor) and TYR (tyrosinase), two pivotal genes in melanogenesis. Importantly, KL increases phagocytosis in cultured RPE by inducing gene expression of MERTK/AXL/TYRO3. These effects of KL are mediated through cAMP-PKA-dependent phosphorylation of transcription factor CREB. In cultured human RPE, KL increases the l-3,4-dihydroxyphenylalanine synthesis and inhibits vascular endothelial growth factor (VEGF) secretion from basal membrane by inhibiting IGF-1 signaling and VEGF receptor 2 phosphorylation. KL also regulates the expression of stress-related genes in RPE, lowers the production of reactive oxygen species, and thereby, protects RPE from oxidative stress. Together, our results demonstrate a critical function for KL in mouse retinal health in vivo, and a protective role toward human RPE cells in vitro. We conclude that KL is an important regulator of RPE homeostasis, and propose that an age-dependent decline of KL expression may contribute to RPE degeneration and retinal pathology.

Indexed as

AnimalsCell LineGene Expression RegulationGlucuronidaseHumansImmunoblottingImmunohistochemistryImmunoprecipitationKlotho ProteinsMass SpectrometryMiceMice, Inbred C57BLMice, KnockoutOxidative StressReal-Time Polymerase Chain ReactionRetinal DegenerationGlucuronidaseKlotho Proteins

Identifiers

PMID24107965
PMCPMC3810551
OpenAlexW2034781464

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.