PRPF8-associated retinitis pigmentosa variant induces human
neural retina-autonomous photoreceptor defects

J 2026

PRPF8-associated retinitis pigmentosa variant induces human neural retina-autonomous photoreceptor defects

ZIMMANN, Felix; Poulami BANIK; Jan KUBOVCIAK; Mathys DELATTRE; Prasoon K THAKUR et al.

Základní údaje

Originální název

PRPF8-associated retinitis pigmentosa variant induces human neural retina-autonomous photoreceptor defects

Autoři

ZIMMANN, Felix; Poulami BANIK; Jan KUBOVCIAK; Mathys DELATTRE; Prasoon K THAKUR; Martin CAPEK; Michal KOLAR; Eva HRUBÁ; Robert DOBROVOLNY; Zuzana CVACKOVA; Tomáš BÁRTA a David STANEK

Vydání

Nature Scientific Reports, Berlin, NATURE RESEARCH, 2026, 2045-2322

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.900 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

PRPF8; retinitis pigmentosa; photoreceptor degeneration; neural retina; genetic variant

Štítky

14110517, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 5. 2026 14:27, Mgr. Tereza Miškechová

Anotace

V originále

Retinitis pigmentosa (RP) is an inherited retinal disorder characterized by the progressive loss of photoreceptors that currently lacks effective treatment. Here, we investigated the effects of the PRPF8-Y2334N variant on neural retina cells using human induced pluripotent stem cell (hiPSC)-derived retinal organoids. Expression of PRPF8-Y2334N variant resulted in photoreceptor defects, including thinning of the outer segment layer. This indicates that the neural retina is impacted independently of retinal pigment epithelium (RPE). At the molecular level, we observed relatively minor changes in mRNA expression in multiple retinal cells. We also found splicing alterations in genes associated with neural and retinal diseases, including those involved in intraflagellar transport, suggesting that these genes may represent common targets of splicing factor mutations. Finally, we detected the misexpression of several circular RNAs (circRNAs), which could serve as early biomarkers of splicing defects caused by RP mutations. Together, we present a model of RP that recapitulates photoreceptor degeneration and demonstrates that these defects are independent of RPE degeneration.

Návaznosti

EF18_046/0016045, projekt VaV

Název: Modernizace národní infrastruktury pro biologické a medicínské zobrazování Czech-BioImaging

EH22_008/0004575, projekt VaV

Název: RNA pro terapii

EH23_015/0008205, projekt VaV

Název: Modernizace VVI Czech-BioImaging

LM2023050, projekt VaV

Název: Národní infrastruktura pro biologické a medicínské zobrazování

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Czech BioImaging: Národní výzkumná infrastruktura pro biologické a medicínské zobrazování

LM2023055, projekt VaV

Název: Česká národní infrastruktura pro biologická data

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, ELIXIR-CZ: Česká národní infrastruktura pro biologická data

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

Citovat

ZIMMANN, Felix; Poulami BANIK; Jan KUBOVCIAK; Mathys DELATTRE; Prasoon K THAKUR; Martin CAPEK; Michal KOLAR; Eva HRUBÁ; Robert DOBROVOLNY; Zuzana CVACKOVA; Tomáš BÁRTA a David STANEK. PRPF8-associated retinitis pigmentosa variant induces human neural retina-autonomous photoreceptor defects. Nature Scientific Reports. Berlin: NATURE RESEARCH, 2026, roč. 16, č. 1, s. 1-14. ISSN 2045-2322. Dostupné z: https://doi.org/10.1038/s41598-026-40376-y.

@article{2570619,
   author = {Zimmann, Felix and Banik, Poulami and Kubovciak, Jan and Delattre, Mathys and Thakur, Prasoon K and Capek, Martin and Kolar, Michal and Hrubá, Eva and Dobrovolny, Robert and Cvackova, Zuzana and Bárta, Tomáš and Stanek, David},
   article_location = {Berlin},
   article_number = {1},
   doi = {https://doi.org/10.1038/s41598-026-40376-y},
   keywords = {PRPF8; retinitis pigmentosa; photoreceptor degeneration; neural retina; genetic variant},
   language = {eng},
   issn = {2045-2322},
   journal = {Nature Scientific Reports},
   title = {PRPF8-associated retinitis pigmentosa variant induces human neural retina-autonomous photoreceptor defects},
   url = {https://www.nature.com/articles/s41598-026-40376-y},
   volume = {16},
   year = {2026}
}

TY  - JOUR
ID  - 2570619
AU  - Zimmann, Felix - Banik, Poulami - Kubovciak, Jan - Delattre, Mathys - Thakur, Prasoon K - Capek, Martin - Kolar, Michal - Hrubá, Eva - Dobrovolny, Robert - Cvackova, Zuzana - Bárta, Tomáš - Stanek, David
PY  - 2026
TI  - PRPF8-associated retinitis pigmentosa variant induces human neural retina-autonomous photoreceptor defects
JF  - Nature Scientific Reports
VL  - 16
IS  - 1
SP  - 1-14
EP  - 1-14
PB  - NATURE RESEARCH
SN  - 20452322
KW  - PRPF8
KW  - retinitis pigmentosa
KW  - photoreceptor degeneration
KW  - neural retina
KW  - genetic variant
UR  - https://www.nature.com/articles/s41598-026-40376-y
N2  - Retinitis pigmentosa (RP) is an inherited retinal disorder characterized by the progressive loss of photoreceptors that currently lacks effective treatment. Here, we investigated the effects of the PRPF8-Y2334N variant on neural retina cells using human induced pluripotent stem cell (hiPSC)-derived retinal organoids. Expression of PRPF8-Y2334N variant resulted in photoreceptor defects, including thinning of the outer segment layer. This indicates that the neural retina is impacted independently of retinal pigment epithelium (RPE). At the molecular level, we observed relatively minor changes in mRNA expression in multiple retinal cells. We also found splicing alterations in genes associated with neural and retinal diseases, including those involved in intraflagellar transport, suggesting that these genes may represent common targets of splicing factor mutations. Finally, we detected the misexpression of several circular RNAs (circRNAs), which could serve as early biomarkers of splicing defects caused by RP mutations. Together, we present a model of RP that recapitulates photoreceptor degeneration and demonstrates that these defects are independent of RPE degeneration.
ER  -

ZIMMANN, Felix; Poulami BANIK; Jan KUBOVCIAK; Mathys DELATTRE; Prasoon K THAKUR; Martin CAPEK; Michal KOLAR; Eva HRUBÁ; Robert DOBROVOLNY; Zuzana CVACKOVA; Tomáš BÁRTA a David STANEK. PRPF8-associated retinitis pigmentosa variant induces human neural retina-autonomous photoreceptor defects. \textit{Nature Scientific Reports}. Berlin: NATURE RESEARCH, 2026, roč.~16, č.~1, s.~1-14. ISSN~2045-2322. Dostupné z: https://doi.org/10.1038/s41598-026-40376-y.

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