Evidence map›Paper›PMID 26193917›Full record

ArticleInvestigative ophthalmology & visual science2015

Systemic and Intravitreal Delivery of Dendrimers to Activated Microglia/Macrophage in Ischemia/Reperfusion Mouse Retina.

Siva P Kambhampati, Alexander J M Clunies-Ross, Imran Bhutto, Manoj K Mishra, Malia Edwards, D Scott McLeod, Rangaramanujam M Kannan, Gerard Lutty

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

Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

50 citing papers in PubMed, 95 citations in OpenAlex.

  1. Review
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  5. Inhibition of microglial glutaminase alleviates chronic stress-induced neurobehavioral and cognitive deficits.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
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  8. Review
  9. Review
  10. Histochemistry for Molecular Imaging in Nanomedicine.International journal of molecular sciences · 2024
    Review
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  12. Review
  13. Article
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  15. Article
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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.

Siva P KambhampatiDepartment of Ophthalmology Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, United States 2Department of Biomedical Engineering, Wayne State University, Detroit, Michigan, United States.
Alexander J M Clunies-RossDepartment of Ophthalmology Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, United States.
Imran BhuttoDepartment of Ophthalmology Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, United States.
Manoj K MishraDepartment of Ophthalmology Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, United States.
Malia EdwardsDepartment of Ophthalmology Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, United States.
D Scott McLeodDepartment of Ophthalmology Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, United States.
Rangaramanujam M KannanDepartment of Ophthalmology Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, United States.
Gerard LuttyDepartment of Ophthalmology Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, United States.
Johns Hopkins University · USJohns Hopkins Hospital · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Jiang Qian · 1985 to 2026
$22.1M
Inflammatory cells of choroid: a therapeutic target in AMD.R01EY016151 · NEI · JOHNS HOPKINS UNIVERSITY · PI EDWARDS, MALIA MICHELLE · 2006 to 2024
$8.0M
Vasculogenesis and hyperoxia in the developing retina.R01EY009357 · NEI · JOHNS HOPKINS UNIVERSITY · PI LUTTY, GERARD ANTHONY · 1993 to 2014
$5.3M
Pluripotent Stem Cell Vascular Therapies for Ischemic RetinopathiesR01EY023962 · NEI · JOHNS HOPKINS UNIVERSITY · PI ZAMBIDIS, ELIAS T. · 2014 to 2018
$1.8M
Systemic nanotherapies for ocular inflammation and choroidal neovascularization.R01EY025304 · NEI · JOHNS HOPKINS UNIVERSITY · PI RANGARAMANUJAM, KANNAN · 2015 to 2018
$1.6M
NEI NIH HHS EY016151NEI NIH HHS EY01765NEI NIH HHS EY025304NEI NIH HHS EY09357NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY009357NEI NIH HHS R01 EY016151NEI NIH HHS R01 EY023962NEI NIH HHS R01 EY025304
6 · The paper itself

Abstract

purposeMicroglial activation and associated neuroinflammation play a key role in the pathogenesis of many diseases of the retina, including viral infection, diabetes, and retinal degeneration. Strategies to target activated microglia and macrophages and attenuate inflammation may be valuable in treating these diseases. We seek to develop dendrimer-based formulations that target retinal microglia and macrophages in a pathology-dependent manner, and deliver drugs, either intravenously or intravitreally.

methodsRetinal uptake of cyanine dye (Cy5)-conjugated dendrimer (D-Cy5) was assessed in normal and ischemia/reperfusion (I/R) mouse eyes. Microglia/macrophage uptake of the dendrimer was assessed with immunofluorescence using rabbit Iba-1 antibody with Cy3-tagged secondary antibody (microglia/macrophage). Uptake in retina and other organs was quantified using fluorescence spectroscopy.

resultsClearance of D-Cy5 from normal eyes was almost complete by 72 hours after intravitreal injection and 24 hours after intravenous delivery. In eyes with activated microglia after I/R injury, D-Cy5 was retained by activated microglia/macrophage (Iba1+ cells) up to 21 days after intravitreal and intravenous administration. In I/R eyes, the relative retention of intravitreal and intravenous D-Cy5 was comparable, if a 30-fold higher intravenous dose was used.

conclusionsIntravitreal and systemic dendrimers target activated microglia and show qualitatively similar retinal biodistribution when administered by either route. Results provide proof-of-concept insights for developing dendrimer drug formulations as treatment options for retinal diseases associated with microglia or macrophage activation such as age-related macular degeneration, diabetic retinopathy, and retinal degenerations.

Indexed as

AnimalsCarbocyaninesDendrimersImmunohistochemistryInjections, IntravenousIntravitreal InjectionsMacrophagesMaleMiceMice, Inbred BALB CMicrogliaMicroscopy, ConfocalNylonsReperfusion InjuryRetinal DiseasesRetinal NeuronsCarbocyaninescyanine dye 5DendrimersNylonsPAMAM-G4

Identifiers

PMID26193917
PMCPMC4510469
OpenAlexW1552284276

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.