Evidence map›Paper›PMID 25205867›Full record

ArticleInvestigative ophthalmology & visual science2014

Overexpression of HtrA1 and exposure to mainstream cigarette smoke leads to choroidal neovascularization and subretinal deposits in aged mice.

Mao Nakayama, Daisuke Iejima, Masakazu Akahori, Junzo Kamei, Asako Goto, Takeshi Iwata

Open access · bronzeAbstract read
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In one paragraph

Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

43 citing papers in PubMed, 70 citations in OpenAlex.

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    Review
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  11. Modeling complex age-related eye disease.Progress in retinal and eye research · 2024
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  18. Current Views on Chr10q26 Contribution to Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2023
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Mao NakayamaDivision of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Daisuke IejimaDivision of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Masakazu AkahoriDivision of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Junzo KameiDepartment of Pathophysiology and Therapeutics, Hoshi University, Tokyo, Japan.
Asako GotoDivision of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Takeshi IwataDivision of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Tokyo Medical Center · JPHoshi University · JPNational Hospital Organization · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeWe determined the function of ARMS2 and HtrA1 in the choroid and retina using transgenic (Tg) mice and evaluated the effects of mainstream cigarette smoke on these mice.

methodsThe chicken actin promoter (CAG) was used to drive mouse HtrA1, human ARMS2, and ARMS2 (A69S) expression in the entire body of a mouse for one year. Fundus observations were performed with a Spectralis HRA+ optical coherence tomograph (OCT). Eyes were sectioned, stained with hematoxylin and eosin (H&E), and analyzed with immunohistochemistry. Mice were exposed to cigarette smoke for 30 min/d, 5 d/wk for 12 weeks using a mainstream smoking chamber (INH06-CIGR02A, MIPS). After 12 weeks, fundus observations and pathological analyses were performed.

resultsApproximately 18.2% of 12-month-old HtrA1 Tg mice exhibited choroidal neovascularization (CNV) by OCT and positive immunostaining with anti-CD31 and anti-fibronectin antibodies. Furthermore, elastic van Gieson (EVG) staining showed Bruch's membrane damage in HtrA1 Tg mice. No retinal changes were observed in ARMS2 and ARMS2 (A69S) Tg mice. A total of 12 weeks of exposure to mainstream cigarette smoke led to CNV rates of 7.7% for wild type (Wt) mice and 20% for HtrA1 Tg mice, but had no effect on ARMS2 Tg mice. In addition, abnormal deposits were observed between photoreceptor cells and the RPE in an HtrA1 Tg mouse exposed to mainstream cigarette smoke.

conclusionsThe HtrA1 overexpression and mainstream cigarette smoke can independently lead to CNV. The HtrA1 gene is a strong risk factor for wet AMD, but not all of the HtrA1 Tg mice developed CNV, suggesting that CNV development depends on multiple risk factors.

Indexed as

Gene Expression RegulationAnimalsBlotting, WesternBruch MembraneChoroidal NeovascularizationFluorescein AngiographyFundus OculiHigh-Temperature Requirement A Serine Peptidase 1HumansImmunohistochemistryMiceMice, Inbred C57BLMicroscopy, Electron, TransmissionProteinsReal-Time Polymerase Chain ReactionRetinaARMS2 protein, humanHigh-Temperature Requirement A Serine Peptidase 1HtrA1 protein, mouseProteinsRNASerine EndopeptidasesTobacco Smoke Pollutionage-related macular degenerationARMS2CNVHtrA1transgenic mouse

Identifiers

PMID25205867
OpenAlexW2332278200

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.