Evidence map›Paper›PMID 37838654›Full record

ArticleImmunity & ageing : I & A2023

Microglia preserve visual function loss in the aging retina by supporting retinal pigment epithelial health.

Margarete M Karg, May Moorefield, Emma Hoffmann, Hannah Philipose, Drenushe Krasniqi, Cindy Hoppe, Daisy Y Shu, Shintaro Shirahama, Bruce R Ksander, Magali Saint-Geniez

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Immunity & ageing : I & A, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Characterization of the ocular inflammatory response to AAV reveals divergence by sex and age.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Margarete M KargSchepens Eye Research Institute of Mass Eye and Ear, 20 Staniford St, Boston, MA, 02114, USA.
May MoorefieldSchepens Eye Research Institute of Mass Eye and Ear, 20 Staniford St, Boston, MA, 02114, USA.
Emma HoffmannSchepens Eye Research Institute of Mass Eye and Ear, 20 Staniford St, Boston, MA, 02114, USA.
Hannah PhiliposeSchepens Eye Research Institute of Mass Eye and Ear, 20 Staniford St, Boston, MA, 02114, USA.
Drenushe KrasniqiSchepens Eye Research Institute of Mass Eye and Ear, 20 Staniford St, Boston, MA, 02114, USA.
Cindy HoppeSchepens Eye Research Institute of Mass Eye and Ear, 20 Staniford St, Boston, MA, 02114, USA.
Daisy Y ShuSchepens Eye Research Institute of Mass Eye and Ear, 20 Staniford St, Boston, MA, 02114, USA.
Shintaro ShirahamaSchepens Eye Research Institute of Mass Eye and Ear, 20 Staniford St, Boston, MA, 02114, USA.
Bruce R Ksander *Schepens Eye Research Institute of Mass Eye and Ear, 20 Staniford St, Boston, MA, 02114, USA. Bruce_Ksander@meei.harvard.edu.
Magali Saint-Geniez *Schepens Eye Research Institute of Mass Eye and Ear, 20 Staniford St, Boston, MA, 02114, USA.
Smith-Kettlewell Eye Research Institute · USMassachusetts Eye and Ear Infirmary · USHarvard University · US

Funding

VISION RESEARCHP30EY003790 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI Patricia Ann D'Amore · 1985 to 2026
$25.5M
NEI NIH HHS P30 EY003790
6 · The paper itself

Abstract

backgroundIncreased age is a risk factor for the development and progression of retinal diseases including age-related macular degeneration (AMD). Understanding the changes that occur in the eye due to aging is important in enhancing our understanding of AMD pathogenesis and the development of novel AMD therapies. Microglia, the resident brain and retinal immune cells are associated with both maintaining homeostasis and protection of neurons and loss of microglia homeostasis could be a significant player in age related neurodegeneration. One important characteristic of retinal aging is the migration of microglia from the inner to outer retina where they reside in the subretinal space (SRS) in contact with the retinal pigment epithelial (RPE) cells. The role of aged subretinal microglia is unknown. Here, we depleted microglia in aged C57/BL6 mice fed for 6 weeks with a chow containing PLX5622, a small molecule inhibitor of colony-stimulating factor-1 receptor (Csf1r) required for microglial survival.

resultsThe subretinal P2RY12 + microglia in aged mice displayed a highly amoeboid and activated morphology and were filled with autofluorescence droplets reminiscent of lipofuscin. TEM indicates that subretinal microglia actively phagocytize shed photoreceptor outer segments, one of the main functions of retinal pigmented epithelial cells. PLX5622 treatment depleted up to 90% of the retinal microglia and was associated with significant loss in visual function. Mice on the microglia depletion diet showed reduced contrast sensitivity and significantly lower electroretinogram for the c-wave, a measurement of RPE functionality, compared to age-matched controls. The loss of c-wave coincided with a loss of RPE cells and increased RPE swelling in the absence of microglia.

conclusionsWe conclude that microglia preserve visual function in aged mice and support RPE cell function, by phagocytosing shed photoreceptor outer segments and lipids, therefore compensating for the known age-related decline of RPE phagocytosis.

Indexed as

Csf1r inhibitorMicrogliaPLX5622RetinaRPEVisual function

Identifiers

PMID37838654
PMCPMC10576380
OpenAlexW4387640957

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.