Evidence map›Paper›PMID 22786897›Full record

ArticleInvestigative ophthalmology & visual science2012

Antibody-mediated retinal pericyte injury: implications for diabetic retinopathy.

Yan Li, Dawn Smith, Qing Li, Nader Sheibani, Suber Huang, Timothy Kern, Ram H Nagaraj, Feng Lin

Open access · bronzeAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

20 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Review
  3. Incidence of diabetic retinopathy in anti-tnf treated rheumatic disease patients with type 2 diabetes.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024
    Article
  4. The innate immune system in diabetic retinopathy.Progress in retinal and eye research · 2021
    Review
  5. Article
  6. Review
  7. Review
  8. Role of Complement in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy.Journal of immunology (Baltimore, Md. : 1950) · 2018
    Article
  9. DesigningFrontiers in aging neuroscience · 2018
    Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Proteasome Activators, PA28International journal of nephrology · 2016
    Article
  16. Article
  17. Review
  18. Review
  19. Future Vision 2020 and Beyond-5 Critical Trends in Eye Research.Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)
    Review
  20. Diabetes and retinal vascular dysfunction.Journal of ophthalmic & vision research
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Yan LiDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Dawn Smith
Qing Li
Nader Sheibani
Suber Huang
Timothy Kern
Ram H Nagaraj
Feng Lin
Case Western Reserve University · USUniversity of Wisconsin–Madison · US

Funding

TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7M
UW Vision Research Core - Administrative CoreP30EY016665 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI ROBERT W NICKELLS · 2005 to 2026
$12.6M
Synergy between T cells and Complement in EAER01NS052471 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI LIN, FENG C · 2005 to 2010
$1.3M
Role of SUSD4 in Retinal Development and FunctionR21EY020956 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI LIN, FENG C · 2010 to 2010
$236k
NEI NIH HHS EY020956NEI NIH HHS P30 EY011373NEI NIH HHS P30 EY016665NEI NIH HHS P30 EY11373NEI NIH HHS R21 EY020956NINDS NIH HHS NS052471NINDS NIH HHS R01 NS052471
6 · The paper itself

Abstract

purposeTo test the hypothesis that autoantibodies against retinal pericytes could develop in diabetic retinopathy, and that these autoantibodies could induce retinal pericyte dysfunction/death via complement.

methodsHuman primary retinal pericytes cultured in media containing normal (5 mM) or high (30 mM) glucose concentrations were incubated with normal human sera in the presence of a retinal pericyte-reactive antibody, then their viability was assessed by a BCECF-based cytotoxicity assay, and their function was assessed by a T-cell proliferation assay. The pericytes were also analyzed by RT-PCR and flow cytometry to detect CD38, an established diabetes-associated cell surface autoantigen. The potential of the anti-CD38 antibodies in inducing pericyte cellular injury was evaluated using the same cytotoxicity assays. In addition, autoantibody-mediated cytotoxicity in mouse retinal pericytes sensitized by sera from mice with developing diabetic retinopathy or control normal mice were also studied.

resultsRetinal pericyte-reactive antibodies induced cellular damage by activating complement in the serum. The antibody-injured pericytes had reduced efficacy in inhibiting T cells. Hyperglycemic culture conditions rendered pericytes more susceptible to antibody-mediated attack. CD38 was expressed in retinal pericytes, and upregulated by TNF-α and IFN-γ, and anti-CD38 antibodies induced pericyte cytotoxicity. Retinal pericytes sensitized with sera from chronic diabetic mice suffered significantly augmented cytotoxicity compared with those sensitized with sera from the control mice.

conclusionsThe autoantibody-initiated complement activation could be a mechanism underlying the loss of function, and eventually, death of retinal pericytes in diabetic patients, suggesting that inhibiting complement activation could be a novel therapeutic approach.

Indexed as

ADP-ribosyl Cyclase 1AdultAgedAnimalsAutoantibodiesAutoantigensCells, CulturedComplement System ProteinsDiabetic RetinopathyHumansHyperglycemiaImmune ToleranceImmunoglobulin GMiceMice, Inbred C57BLPericytesADP-ribosyl Cyclase 1AutoantibodiesAutoantigensComplement System ProteinsImmunoglobulin G

Identifiers

PMID22786897
PMCPMC3419006
OpenAlexW2047810552

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.