Single-cell analysis reveals inflammatory interactions driving macular degeneration
Manik Kuchroo, Marcello DiStasio, Eric Song, Eda Calapkulu, Le Zhang, Maryam Ige, Amar H Sheth, Abdelilah Majdoubi et al.. Nature communications, 2023-05-05
Topic: Inflammation, microglia and astrocytes
Due to commonalities in pathophysiology, age-related macular degeneration (AMD) represents a uniquely accessible model to investigate therapies for neurodegenerative diseases, leading us to examine whether pathways of disease progression are shared across neurodegenerative conditions. Here we use single-nucleus RNA sequencing to profile lesions from 11 postmortem human retinas with age-related macular degeneration and 6 control retinas with no history of retinal disease. We create a machine-learning pipeline based on recent advances in data geometry and topology and identify activated glial populations enriched in the early phase of disease. Examining single-cell data from Alzheimer's disease and progressive multiple sclerosis with our pipeline, we find a similar glial activation profile enriched in the early phase of these neurodegenerative diseases. In late-stage age-related macular degeneration, we identify a microglia-to-astrocyte signaling axis mediated by interleukin-1β which drives angiogenesis characteristic of disease pathogenesis. We validated this mechanism using in vitro and in vivo assays in mouse, identifying a possible new therapeutic target for AMD and possibly other neurodegenerative conditions. Thus, due to shared glial states, the retina provides a potential system for investigating therapeutic approaches in neurodegenerative diseases.
Key findings
- We create a machine-learning pipeline based on recent advances in data geometry and topology and identify activated glial populations enriched in the early phase of disease.
- Examining single-cell data from Alzheimer's disease and progressive multiple sclerosis with our pipeline, we find a similar glial activation profile enriched in the early phase of these neurodegenerative diseases.
- In late-stage age-related macular degeneration, we identify a microglia-to-astrocyte signaling axis mediated by interleukin-1β which drives angiogenesis characteristic of disease pathogenesis.
- We validated this mechanism using in vitro and in vivo assays in mouse, identifying a possible new therapeutic target for AMD and possibly other neurodegenerative conditions.
- Thus, due to shared glial states, the retina provides a potential system for investigating therapeutic approaches in neurodegenerative diseases.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 25 of the 56 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37147305) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 25 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 25 of the 56 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Kuchroo, M., DiStasio, M., Song, E., Calapkulu, E., Zhang, L., Ige, M., et al. (2023). Single-cell analysis reveals inflammatory interactions driving macular degeneration. Nature communications. https://doi.org/10.1038/s41467-023-37025-7
Vancouver
Kuchroo M, DiStasio M, Song E, Calapkulu E, Zhang L, Ige M, et al. Single-cell analysis reveals inflammatory interactions driving macular degeneration. Nature communications. 2023. doi:10.1038/s41467-023-37025-7. PMID: 37147305.
BibTeX
@article{kuchroo2023-37147305,
author = {Kuchroo, Manik and DiStasio, Marcello and Song, Eric and Calapkulu, Eda and Zhang, Le and Ige, Maryam and Sheth, Amar H and Majdoubi, Abdelilah and others},
title = {{Single-cell analysis reveals inflammatory interactions driving macular degeneration}},
journal = {Nature communications},
year = {2023},
doi = {10.1038/s41467-023-37025-7},
pmid = {37147305},
url = {https://doi.org/10.1038/s41467-023-37025-7}
}
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