Evidence map›Paper›PMID 38942762›Full record

ArticleCell death discovery2024

Mechanisms contributing to inhibition of retinal ganglion cell death by cell permeable peptain-1 under glaucomatous stress.

Gretchen A Johnson, Bindu Kodati, Rooban B Nahomi, Jennifer H Pham, Vignesh R Krishnamoorthy, Nicole R Phillips, Raghu R Krishnamoorthy, Ram H Nagaraj, Dorota L Stankowska

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

9 authors.

Gretchen A Johnson *North Texas Eye Research Institute, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA.
Bindu Kodati *North Texas Eye Research Institute, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA.
Rooban B NahomiDepartment of Ophthalmology, School of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA.
Jennifer H PhamNorth Texas Eye Research Institute, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA.
Vignesh R KrishnamoorthyDepartment of Cell and Molecular Physiology, Loyola University, Maywood, IL, USA.
Nicole R PhillipsDepartment of Microbiology, Immunology, and Genetics, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA.
Raghu R KrishnamoorthyNorth Texas Eye Research Institute, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA.
Ram H NagarajDepartment of Ophthalmology, School of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA.
Dorota L StankowskaNorth Texas Eye Research Institute, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA. dorota.stankowska@unthsc.edu.ORCID http://orcid.org/0000-0002-2541-6649

Funding

Mechanisms underlying endothelin mediated neurodegeneration in glaucomaR01EY028179 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI KRISHNAMOORTHY, RAGHU R · 2017 to 2025
$2.9M
NEI NIH HHS R01 EY028179Research to Prevent Blindness (RPB) Gates Grubstake AwardU.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) R01EY028179
6 · The paper itself

Abstract

This study assesses the neuroprotective potential of CPP-P1, a conjugate of an anti-apoptotic peptain-1 (P1) and a cell-penetrating peptide (CPP) in in vitro, in vivo, and ex vivo glaucoma models. Primary retinal ganglion cells (RGCs) were subjected to either neurotrophic factor (NF) deprivation for 48 h or endothelin-3 (ET-3) treatment for 24 h and received either CPP-P1 or vehicle. RGC survival was analyzed using a Live/Dead assay. Axotomized human retinal explants were treated with CPP-P1 or vehicle for seven days, stained with RGC marker RBPMS, and RGC survival was analyzed. Brown Norway (BN) rats with elevated intraocular pressure (IOP) received weekly intravitreal injections of CPP-P1 or vehicle for six weeks. RGC function was evaluated using a pattern electroretinogram (PERG). RGC and axonal damage were also assessed. RGCs from ocular hypertensive rats treated with CPP-P1 or vehicle for seven days were isolated for transcriptomic analysis. RGCs subjected to 48 h of NF deprivation were used for qPCR target confirmation. NF deprivation led to a significant loss of RGCs, which was markedly reduced by CPP-P1 treatment. CPP-P1 also decreased ET-3-mediated RGC death. In ex vivo human retinal explants, CPP-P1 decreased RGC loss. IOP elevation resulted in significant RGC loss in mid-peripheral and peripheral retinas compared to that in naive rats, which was significantly reduced by CPP-P1 treatment. PERG amplitude decline in IOP-elevated rats was mitigated by CPP-P1 treatment. Following IOP elevation in BN rats, the transcriptomic analysis showed over 6,000 differentially expressed genes in the CPP-P1 group compared to the vehicle-treated group. Upregulated pathways included CREB signaling and synaptogenesis. A significant increase in Creb1 mRNA and elevated phosphorylated Creb were observed in CPP-P1-treated RGCs. Our study showed that CPP-P1 is neuroprotective through CREB signaling enhancement in several settings that mimic glaucomatous conditions. The findings from this study are significant as they address the pressing need for the development of efficacious therapeutic strategies to maintain RGC viability and functionality associated with glaucoma.

Identifiers

PMID38942762
PMCPMC11213865

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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.