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

J 2025

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

POLEŠOVSKÁ, Lada; Simona TRMAČOVÁ; Canan ÇELIKER; Eva HRUBÁ; Francisco MOLINA GAMBIN et al.

Základní údaje

Originální název

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

Autoři

POLEŠOVSKÁ, Lada; Simona TRMAČOVÁ; Canan ÇELIKER; Eva HRUBÁ; Francisco MOLINA GAMBIN; Václav CHOCHOLA ; Veronika MATUŠKOVÁ ; Eleni BELI a Tomáš BÁRTA

Vydání

CELL DEATH & DISEASE, LONDON, NATURE PUBLISHING GROUP, 2025, 2041-4889

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 9.600 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

diabetic retinopathy; human retinal organoids; hyperglycaemia; photoreceptor degeneration; oxidative stress

Štítky

14110219, 14110517, CF BIOIT, CF CELLIM, CF GEN, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 16. 3. 2026 08:00, Mgr. Tereza Miškechová

Anotace

V originále

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 & 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.

Návaznosti

MUNI/A/1738/2024, interní kód MU

Název: Zdroje pro tkáňové inženýrství 15

Investor: Masarykova univerzita, Zdroje pro tkáňové inženýrství 15

MUNI/LF-SUp/1197/2022, interní kód MU

Název: Retinální organoidy jako nástroj pro studium embryonální diabetické retinopatie.

Investor: Masarykova univerzita, Retinální organoidy jako nástroj pro studium embryonální diabetické retinopatie., Start-up

NU22-07-00380, projekt VaV

Název: Aplikace retinálních buněk a organoidů ve funkční diagnostice a léčbě ztráty zraku u Bardet-Biedlova syndromu

Investor: Ministerstvo zdravotnictví ČR, Aplikace retinálních buněk a organoidů ve funkční diagnostice a léčbě ztráty zraku u Bardet-Biedlova syndromu, Podprogram 1 - standardní

101059788, interní kód MU

Název: Central European Advanced Therapy and Immunotherapy Centre

Investor: Evropská unie, Central European Advanced Therapy and Immunotherapy Centre, Rozšiřování účasti a posílení ERA

90250, velká výzkumná infrastruktura

Název: Czech-BioImaging III

90267, velká výzkumná infrastruktura

Název: NCMG III

Citovat

POLEŠOVSKÁ, Lada; Simona TRMAČOVÁ; Canan ÇELIKER; Eva HRUBÁ; Francisco MOLINA GAMBIN; Václav CHOCHOLA; Veronika MATUŠKOVÁ; Eleni BELI a Tomáš BÁRTA. Unveiling the cellular and molecular mechanisms of diabetic retinopathy with human retinal organoids. CELL DEATH & DISEASE. LONDON: NATURE PUBLISHING GROUP, 2025, roč. 16, č. 1, s. 1-13. ISSN 2041-4889. Dostupné z: https://doi.org/10.1038/s41419-025-08244-1.

@article{2544422,
   author = {Polešovská, Lada and Trmačová, Simona and Çeliker, Canan and Hrubá, Eva and Molina Gambin, Francisco and Chochola, Václav and Matušková, Veronika and Beli, Eleni and Bárta, Tomáš},
   article_location = {LONDON},
   article_number = {1},
   doi = {https://doi.org/10.1038/s41419-025-08244-1},
   keywords = {diabetic retinopathy; human retinal organoids; hyperglycaemia; photoreceptor degeneration; oxidative stress},
   language = {eng},
   issn = {2041-4889},
   journal = {CELL DEATH & DISEASE},
   title = {Unveiling the cellular and molecular mechanisms of diabetic retinopathy with human retinal organoids},
   url = {https://www.nature.com/articles/s41419-025-08244-1},
   volume = {16},
   year = {2025}
}

TY  - JOUR
ID  - 2544422
AU  - Polešovská, Lada - Trmačová, Simona - Çeliker, Canan - Hrubá, Eva - Molina Gambin, Francisco - Chochola, Václav - Matušková, Veronika - Beli, Eleni - Bárta, Tomáš
PY  - 2025
TI  - Unveiling the cellular and molecular mechanisms of diabetic retinopathy with human retinal organoids
JF  - CELL DEATH & DISEASE
VL  - 16
IS  - 1
SP  - 1-13
EP  - 1-13
PB  - NATURE PUBLISHING GROUP
SN  - 20414889
KW  - diabetic retinopathy
KW  - human retinal organoids
KW  - hyperglycaemia
KW  - photoreceptor degeneration
KW  - oxidative stress
UR  - https://www.nature.com/articles/s41419-025-08244-1
N2  - 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 & 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.
ER  -

POLEŠOVSKÁ, Lada; Simona TRMAČOVÁ; Canan $\backslash$C CELIKER; Eva HRUBÁ; Francisco MOLINA GAMBIN; Václav CHOCHOLA; Veronika MATUŠKOVÁ; Eleni BELI a Tomáš BÁRTA. Unveiling the cellular and molecular mechanisms of diabetic retinopathy with human retinal organoids. \textit{CELL DEATH \&{} DISEASE}. LONDON: NATURE PUBLISHING GROUP, 2025, roč.~16, č.~1, s.~1-13. ISSN~2041-4889. Dostupné z: https://doi.org/10.1038/s41419-025-08244-1.

Přehled o publikaci