Exploiting New Methods to Study Microglia in Healthy and Diseased Retina

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Background

Microglia are immune-competent cells found in the central nervous system (CNS) and retina. While CNS microglia is implicated in CNS development and homeostasis, the functional role of microglia in the healthy retina is less clear. In pathological conditions, retinal microglia react to proinflammatory insults such as injury, infection, or hypoxia by activating and releasing proinflammatory cytokines, active phagocytosis of cellular debris, and facilitating the recruitment and migration of blood circulating immune cells into the retina. With the retina being a highly specialized and tightly organized tissue, the dysregulation of the microglia response contributes to vision impairment. Furthermore, the increased retinal microglia activation is implicated in neurodegenerative, inflammatory, autoimmune, and neovascular eye conditions such as age macular degeneration, glaucoma, uveoretinitis, and diabetic retinopathy. Conditions that lead to vision impairment and, in some cases, blindness.

With a substantial amount of research conducted in brain microglia, the retinal microglia remains far less explored. The retina microglia research field has undergone rapid development in the recent decade by creating new research tools to study microglia in vivo, ex vivo, and in vitro. New microglia-specific markers, such as TMEM119 and P2ry12 and transgenic animal lines, including CX3CR1-GFP and CX3CR1-Cre, provided the ability to observe the microglia cells' behavior and selectively regulate gene targets within the microglia cells. Refinement of the retinal microglial cells isolation and culture protocols provided the opportunity to conduct mechanistic and functional studies in vitro. Recent advances in single-cell sequencing technologies applied to the retina facilitate discovering the new microglia subpopulations and provide further insights into the microglia homeostatic and pathological roles. New small-molecule treatments (i.e., PLX5622) introduce a microglia ablation approach that allows studying the retina without microglia, microglia repopulation, and replacement, further increasing the retinal microglia origins and knowledge functions. Thus, the goal of this Research Topic is to assemble the most recent knowledge in the retinal microglia field, research methodology and explore retinal microglia's roles in pathology.

We particularly welcome the submission of Original Research, Review, and Methods articles focusing on, but not limited to:
• Studies on microglia roles in the homeostatic and diseased retina (research on retinal microglia role in retinal degeneration and retina inflammatory disorders are particularly encouraged)
• Studies on microglia subpopulations and their functions in the retina.
• Mechanistic studies on pathways involved in retinal microglia regulation and activation
• Improved isolation and culture techniques as reliable isolation and prolonged in vitro culture of retinal microglia remains to be challenging.
• In vivo imaging of microglial cells and it is interaction with retinal neurons
• Proteomics, metabolomics, single-cell sequencing, RNA-seq studies with extra functional analysis.

Keywords: microglia; retina; homeostasis: disease; regulation; cell culture; cell isolation; imaging; omics

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