GEO series

N-acetyl-L-cysteine ethyl ester (NACET) induces the transcription factor NRF2 in the retina and prevents its aging and diabetic retinopathy. [II]

GSE299876 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2026/01/21 Platform GPL18573

At a glance

RNA-seq (gene expression) · human · 18 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 18 samples: 18 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: N-acetyl-l-cysteine ethyl ester (NACET) induces the transcription factor NRF2 and prevents retinal aging and diabetic retinopathyRedox biology · 2025

Summary (written by the submitters)

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are leading causes of visual impairment in older people, with oxidative stress playing a central role in the development of these diseases. In fact, the cells of the retina are particularly susceptible to oxidative damage due to high metabolic activity and exposure to light.

Read the full summary ↓

Glutathione (GSH), a key intracellular antioxidant, is essential for retinal protection but it becomes limited during aging and in diabetes patients. Cysteine (Cys), the rate-limiting precursor for GSH synthesis, can be supplemented by derivatives such as N-acetylcysteine ethyl ester (NACET), which has better bioavailability and cellular uptake compared to the widely used N-acetylcysteine (NAC). NACET effectively increases intracellular Cys and GSH levels, improves the viability of retinal pigment epithelium (RPE) cells under oxidative stress and increases in vivo GSH levels after oral administration. In this study, we show that NACET strongly stimulates NRF2 expression and activity in RPE cells, with a distinctive transcriptomic response. Using RNA interference, mass spectrometry and KEAP1 mutagenesis, we identify direct cysteinylation of sensor residues Cys226 and Cys613 on KEAP1 as the molecular mechanism underlying NRF2 activation after NACET treatment. Furthermore, in vivo administration of NACET induces NRF2 activity and increases GSH content in the retina, mitigating oxidative damage in aging and diabetic mouse models. These results position NACET as a promising therapeutic candidate for oxidative stress-related retinal diseases such as AMD and DR by targeting the KEAP1–NRF2–GSH axis.

Published in

N-acetyl-l-cysteine ethyl ester (NACET) induces the transcription factor NRF2 and prevents retinal aging and diabetic retinopathy

Realini G, Amato R, Rasa M et al. · Redox biology 2025 · PMID 41205411 · doi:10.1016/j.redox.2025.103914

This dataset

Open GSE299876 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE299876_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1277212 and SRA study SRP592247. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41205411) ↗

Study design

18 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 18 sample titles: 18 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM9048232 1) ARPE-19 control untreated replicate 1 (ARPE_Ctrl_rep1)
GSM9048233 2) ARPE-19 control untreated replicate 2 (ARPE_Ctrl_rep2)
GSM9048234 3) ARPE-19 control untreated replicate 3 (ARPE_Ctrl_rep3)
GSM9048235 4) ARPE-19 control H2O2-treated replicate 1 (ARPE_ H2O2_rep1)
GSM9048236 5) ARPE-19 control H2O2-treated replicate 2 (ARPE_ H2O2_rep2)
GSM9048237 6) ARPE-19 control H2O2-treated replicate 3 (ARPE_ H2O2_rep3)
GSM9048238 7) ARPE-19 control NACET-treated replicate 1 (ARPE_ NACET_rep1)
GSM9048239 8) ARPE-19 control NACET-treated replicate 2 (ARPE_ NACET_rep2)
GSM9048240 9) ARPE-19 control NACET-treated replicate 3 (ARPE_ NACET_rep3)
GSM9048241 10) ARPE-19 NRF2-edited untreated replicate 1 (C1_Ctrl_rep1)
GSM9048242 11) ARPE-19 NRF2-edited untreated replicate 2 (C1_Ctrl _rep2)
GSM9048243 12) ARPE-19 NRF2-edited untreated replicate 3 (C1_Ctrl_rep3)
GSM9048244 13) ARPE-19 NRF2-edited H2O2-treated replicate 1 (C1_H2O2_rep1)
GSM9048245 14) ARPE-19 NRF2-edited H2O2-treated replicate 2 (C1_H2O2_rep2)
GSM9048246 15) ARPE-19 NRF2-edited H2O2-treated replicate 3 (C1_H2O2_rep3)
GSM9048247 16) ARPE-19 NRF2-edited NACET-treated replicate 1 (C1_NACET_rep1)
GSM9048248 17) ARPE-19 NRF2-edited NACET-treated replicate 2 (C1_NACET_rep2)
GSM9048249 18) ARPE-19 NRF2-edited NACET-treated replicate 3 (C1_NACET_rep3)

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