Evidence map›Paper›PMID 40815371›Full record

ArticleDiabetologia2025

Scavenging acrolein with 2-HDP preserves neurovascular integrity in a rat model of diabetic retinal disease.

Josy Augustine, Evan P Troendle, Thomas Friedel, Caolan Baldwin, Eimear M Byrne, Sadaf Ashraf, Paul Canning, Corey A McAleese, Adam G Rollo, Peter Barabas and 4 more

Abstract read
In one paragraph

Article in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

14 authors.

Josy AugustineWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK.ORCID http://orcid.org/0000-0001-5178-5029
Evan P TroendleWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK.ORCID http://orcid.org/0000-0003-4825-4088
Thomas FriedelWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK.
Caolan BaldwinWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK.ORCID http://orcid.org/0009-0009-6443-7440
Eimear M ByrneWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK.ORCID http://orcid.org/0000-0001-5064-3539
Sadaf AshrafWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK.ORCID http://orcid.org/0000-0001-5592-9122
Paul CanningWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK.ORCID http://orcid.org/0000-0002-0888-0124
Corey A McAleeseWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK.ORCID http://orcid.org/0000-0003-2756-4941
Adam G RolloWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK.ORCID http://orcid.org/0009-0002-4082-8454
Peter BarabasWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK.ORCID http://orcid.org/0000-0002-8166-3476
Timothy J LyonsWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK.ORCID http://orcid.org/0000-0003-2106-1622
Martin B UlmschneiderDepartment of Chemistry, King's College London, London, UK.ORCID http://orcid.org/0000-0001-8103-0516
Alan W StittWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK.ORCID http://orcid.org/0000-0002-8647-9918
Tim M CurtisWellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, UK. t.curtis@qub.ac.uk.ORCID http://orcid.org/0000-0003-1543-2781

Funding

Diabetes UK 18/0005791Health & Social Care R&D Division STL/4748/13Medical Research Council MC_PC_15026
6 · The paper itself

Abstract

aims/hypothesisDiabetic retinal disease (DRD) is characterised by progressive neurovascular unit (NVU) dysfunction, often occurring before visible microvascular damage. Our previous studies suggested that the accumulation of acrolein (ACR)-derived protein adducts on retinal Müller cells and neuronal proteins may contribute to NVU dysfunction in diabetes, although this has yet to be directly tested. In this study, we evaluated the effects of the novel ACR-scavenging drug 2-hydrazino-4,6-dimethylpyrimidine (2-HDP) on retinal NVU dysfunction in experimental diabetes and explored its potential for systemic delivery in humans.

methodsSprague Dawley rats were divided into three groups: non-diabetic rats; streptozocin (STZ)-induced diabetic rats; and STZ-induced diabetic rats treated with 2-HDP in their drinking water throughout the duration of diabetes. Endpoint measures were taken at varying time points, ranging from 1 to 6 months post-diabetes induction. Retinal function and structure were evaluated using electroretinography (ERG) and spectral-domain optical coherence tomography (SD-OCT). Retinal vessel calibre, BP and vasopermeability (assessed by Evans Blue leakage) were also monitored. Immunohistochemistry was employed to assess retinal neurodegenerative and vasodegenerative changes, while cytokine arrays were used to investigate the effect of 2-HDP on diabetes-induced retinal inflammation. The accumulation of the ACR-protein adduct Nε-(3-formyl-3,4-dehydropiperidino)lysine (FDP-Lys) in human diabetic retinas was analysed. Computational chemistry simulations were performed to predict 2-HDP's passive permeability properties and its potential for systemic delivery.

results2-HDP treatment had no effect on blood glucose, body weight, water intake, HbA CONCLUSIONS/

interpretation2-HDP protects against retinal NVU dysfunction in diabetic rats by reducing FDP-Lys accumulation, preserving neuroretinal function and preventing microvascular damage, independent of glycaemic control. These results, combined with evidence from human diabetic retinas and molecular dynamics simulations, support 2-HDP's potential as a promising therapeutic agent for DRD, warranting further preclinical and clinical investigation.

Indexed as

AcroleinDiabetes Mellitus, ExperimentalDiabetic RetinopathyHydrazinesPyrimidinesAnimalsElectroretinographyMaleRatsRats, Sprague-DawleyRetinaRetinal VesselsTomography, Optical CoherenceAcroleinHydrazinesPyrimidines2-Hydrazino-4,6-dimethylpyrimidine (2-HDP)AcroleinDiabetic retinal disease (DRD)Electroretinography (ERG)Molecular dynamics (MD) simulationsNeurodegenerationNeurovascular unit (NVU)Nε-(3-formyl-3,4-dehydropiperidino)lysine (FDP-Lys)Retinal inflammationVascular pathology

Identifiers

PMID40815371
PMCPMC12534245

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