Researchers at Sun Yat-sen University identified a distinct population of lipid-accumulating reactive microglia that drives retinal degeneration, according to a study published in Nature Communications on August 15, 2026. The cells, termed aLARM, localize predominantly to the outer retina and are characterized by elevated expression of the CD36 receptor.
The team used single-cell RNA sequencing and spatial transcriptomics in mice with NaIO3-induced retinal degeneration to isolate the microglial subset. Researchers found that these aLARM cells remain conserved across mouse models as well as human patients. When investigators deleted CD36 specifically within microglia, the genetic edit abolished aLARM-driven inflammation and tissue degeneration. Conversely, subretinal transplantation of CD36-positive aLARM cells accelerated structural damage and functional impairment in the retina.
Mechanistically, CD36-positive aLARM cells activate the NLRP3 inflammasome and release interleukin-1 beta (IL-1β). This cytokine engages IL-1R1 receptors on surrounding microglia, macrophages, pericytes, and smooth muscle cells, creating a feed-forward inflammatory circuit in the tissue. In therapeutic tests, administering the neutralizing antibody FA6-152 to block CD36 reduced the formation of aLARM cells and protected mice against retinal neurodegeneration.
Tian Zhou, Ziqi Yang, and Hong Zhou contributed equally as lead authors on the paper alongside co-authors at the State Key Laboratory of Ophthalmology within the Zhongshan Ophthalmic Center in Guangzhou, China. The research received grant funding from the National Natural Science Foundation of China, the Guangdong Provincial Key Area R&D Program, and the Guangzhou Science and Technology Plan Project.
