Unveiling the cellular and molecular mechanisms of diabetic retinopathy with human retinal organoids

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F25%3A00083333" target="_blank" >RIV/65269705:_____/25:00083333 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/25:00143121

Result on the web

<a href="https://www.nature.com/articles/s41419-025-08244-1" target="_blank" >https://www.nature.com/articles/s41419-025-08244-1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41419-025-08244-1" target="_blank" >10.1038/s41419-025-08244-1</a>

Result language

angličtina

Original language name

Unveiling the cellular and molecular mechanisms of diabetic retinopathy with human retinal organoids

Original language description

Diabetic retinopathy (DR) is a leading cause of vision impairment worldwide, driven by chronic hyperglycaemia and its complex metabolic consequences. While animal models have been widely used to study DR, they often fail to replicate the physiology of the human retina. Here, we employed human retinal organoids to investigate the effects of incremental hyperglycaemic stress-a modest increase from a standard high-glucose baseline (17.5 mM) to 25 mM D-glucose-across different stages of retinal differentiation. Early-stage organoids demonstrated resilience to high-glucose levels, maintaining normal morphology, viability, and gene expression. In contrast, late-stage organoids exhibited marked photoreceptor vulnerability, including downregulation of outer segment (OS)-specific genes, shortened OSs, increased oxidative stress, astrocyte activation, and significantly higher levels of apoptosis. Transcriptomic analysis revealed substantial changes in pathways related to vision, including the G protein-coupled receptor signalling pathway, response to light stimulus, and visual perception. While photoreceptors were particularly vulnerable, other retinal cell types, including bipolar cells, ganglion cells, and M &amp; uuml;ller glia, showed greater resilience. Additionally, glial activation, evidenced by increased expression of astrocyte markers, suggested an adaptive response to hyperglycaemia. To validate our findings, we compared our dataset with publicly available transcriptomic datasets from human retinas with DR, confirming key overlaps in pathways related to photoreceptor dysfunction, gliogenesis, and oxidative stress responses. While this non-vascularised model does not replicate the onset of DR from physiological glucose levels, it provides a human-specific platform for dissecting the molecular mechanisms of neurodegeneration associated with incremental hyperglycaemic stress.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

<a href="/en/project/NU22-07-00380" target="_blank" >NU22-07-00380: Application of retinal cells and organoids in functional diagnostics and treatment of vision loss in Bardet-Biedl syndrome</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cell Death &amp; Disease

ISSN

2041-4889

e-ISSN

2041-4889

Volume of the periodical

16

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

892

UT code for WoS article

001642805500002

EID of the result in the Scopus database

2-s2.0-105025377523