More than meets the eye: The role of microglia in healthy and diseased retina

Abstract

Microglia are the main resident immune cells of the nervous system and as such they are involved in multiple roles ranging from tissue homeostasis to response to insults and circuit refinement. While most knowledge about microglia comes from brain studies, some mechanisms have been confirmed for microglia cells in the retina, the light-sensing compartment of the eye responsible for initial processing of visual information. However, several key pieces of this puzzle are still unaccounted for, as the characterization of retinal microglia has long been hindered by the reduced population size within the retina as well as the previous lack of technologies enabling single-cell analyses. Accumulating evidence indicates that the same cell type may harbor a high degree of transcriptional, morphological and functional differences depending on its location within the central nervous system. Thus, studying the roles and signatures adopted specifically by microglia in the retina has become increasingly important. Here, we review the current understanding of retinal microglia cells in physiology and in disease, with particular emphasis on newly discovered mechanisms and future research directions.

Age-related dysregulation of the retinal transcriptome in African turquoise killifish

“…Müller glia ( glula, rlbp1a ) showed characteristic radial fibre morphology with their nuclei confined to the INL (Figure 3K, Figure S5H), while gfap signal was restricted to their end feet (Figure S5H). The resident immune cells, marked by csf1r , lined the IPL (Figure 3L), as expected for resting microglia/macrophages (Murenu et al, 2022). Notably, in contrast to mammals, we identified oligodendrocytes ( plp1b, cldn19 ), highly abundant in the optic nerve head (Figure S5I) and sparsely distributed throughout the retina in the GCL (Figure 3M, Figure S5I) and the INL (Figure S5I, arrowhead) (Nakazawa et al, 1993; Santos-Ledo et al, 2023).…”

Environmental Risk Factors Associated with Retinochoroiditis Caused by <em>Toxoplasma gondii</em>

“…21 Many studies corroborate that cytokines such as TNF-α, IL-1β, IL-6, and CCL2, and toxic mediators such as NO are directly involved in the regulation of the immune system in ocular toxoplasmosis, some of which act on vascular permeability, recruitment of leukocytes, and retinal inflammation. [27][28][29][30][31][32][33] The reactivation of eye infection caused by T. gondii is frequent because it is an immunologically favorable environment [26,29,31,[34][35][36] and pregnancy is a facilitating factor for its reactivation due to the immunotolerance that it confers on the host. [26,[37][38][39] The T. gondii parasite, when penetrating the human cell, activates several cytokine genes such as IL-10, IL-1β, IFN-γ, which are associated with the development of ocular toxoplasmosis.…”

Polyunsaturated Lipids in the Light-Exposed and Prooxidant Retinal Environment

“…The impact of A2E-derived compounds upon blue light exposure on the alternative complement pathway may interfere with RPE cells’ role in setting the eye immune privilege via the release of several factors that reduce the reactivity of retina immune cells (recently revised by [ 89 , 90 ]). Furthermore, A2E may affect retinal cell viability via its impact on microglial cells, the primary resident immune cells of the nervous system and the retina (recently reviewed by [ 91 ]) that play a role in retinal degenerations caused by genetic defects, as in the case of retinal degeneration 10 mice (Rd10) [ 92 ]. Indeed, A2E has been reported to affect microglial cells, promoting their activation, and decreasing complement factor H expression, thus promoting complement activation.…”