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Although techniques for culturing retinal organoids (ROs) have advanced significantly, they still fall short of incorporating all cell types necessary for maintaining retinal homeostasis, particularly immune cells like microglia. Standardizing the inclusion of immune cells in RO cultures would greatly enhance research into the mechanisms underlying retinal diseases and the discovery of therapeutic targets. This review examines recent advancements in co-culturing ROs with immune cells to mimic the physiological and pathological microenvironments of the retina, focusing on tissue structure and function. Furthermore, it emphasizes the importance of cutting-edge organoid technologies, such as microfluidics and organ-on-chip systems, in propelling research in this field. The goal is to equip researchers with a more profound understanding of microglial ROs and their potential applications in scientific investigations.<\/jats:p>","DOI":"10.3389\/fcell.2025.1574283","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T05:45:37Z","timestamp":1748583937000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["\u201cArmed in-vitro retina\u201d-generating microglial retinal organoids, where are we now?"],"prefix":"10.3389","volume":"13","author":[{"given":"Yaohong","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixiong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaohui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.neuron.2017.03.042","article-title":"iPSC-derived human microglia-like cells to study neurological diseases","volume":"94","author":"Abud","year":"2017","journal-title":"Neuron"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e46188","DOI":"10.7554\/eLife.46188","article-title":"Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform","volume":"8","author":"Achberger","year":"2019","journal-title":"Elife"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2705","DOI":"10.1002\/glia.23880","article-title":"Exosomes derived from microglia exposed to elevated pressure amplify the neuroinflammatory response in retinal cells","volume":"68","author":"Aires","year":"2020","journal-title":"Glia"},{"key":"B4","doi-asserted-by":"publisher","first-page":"101491","DOI":"10.1016\/j.scr.2019.101491","article-title":"Accelerated photoreceptor differentiation of hiPSC-derived retinal organoids by contact co-culture with retinal pigment epithelium","volume":"39","author":"Akhtar","year":"2019","journal-title":"Stem Cell Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1146\/annurev-neuro-111020-090812","article-title":"Challenges of organoid research","volume":"45","author":"Andrews","year":"2022","journal-title":"Annu. 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