Role of myeloid cells in ischemic retinopathies: recent advances and unanswered questions

Abstract

Myeloid cells including microglia and macrophages play crucial roles in retinal homeostasis by clearing cellular debris and regulating inflammation. These cells are activated in several blinding ischemic retinal diseases including diabetic retinopathy, where they may exert both beneficial and detrimental effects on neurovascular function and angiogenesis. Myeloid cells impact the progression of retinal pathologies and recent studies suggest that targeting myeloid cells is a promising therapeutic strategy to mitigate diabetic retinopathy and other ischemic retinal diseases. This review summarizes the recent advances in our understanding of the role of microglia and macrophages in retinal diseases and focuses on the effects of myeloid cells on neurovascular injury and angiogenesis in ischemic retinopathies. We highlight gaps in knowledge and advocate for a more detailed understanding of the role of myeloid cells in retinal ischemic injury to fully unlock the potential of targeting myeloid cells as a therapeutic strategy for retinal ischemia.

Role of inflammation in a rat model of radiation retinopathy

“…However, their shape was conserved, and it appeared that the body of an Iba1-positive cell filled the shape of the missing RPE cell. Microglial cells lying on the RPE have already been described in various ocular diseases, such as AMD with choroidal neovascularization [ 8 , 66 ], diabetic retinopathy [ 67 ] and RPE injury, but this type of cell shape has never been described so far. Iba1 cells can be recruited to the injured area, but the replacement of RPE cells remains obscure.…”

“…This raises the question of whether the microglia proliferate once in the subretinal space or the cells are non-proliferative, and the recruitment is constant and possibly increasing, which would explain the accumulation of these cells in the outer retina. The role of microglia also seems to depend on the presence or absence of other types of inflammatory cells, such as infiltrating monocytes, as well as on the cytokines and inflammatory or anti-inflammatory factors they can produce [ 8 ]. As they can also produce VEGF in response to necrotic RPE to contribute to angiogenic development [ 68 , 69 ], it would be interesting to study angiogenic markers such as VEGF and angiopoietin 1 and 2 or their receptor Tie2 since vascular proliferative complications are common features observed in RR.…”

“…The slow turnover of endothelial cells could explain the late onset and progressive development of RR. The role of retinal inflammation has been characterized in several retinal disorders, including diabetic retinopathy [ 8 – 10 ] and age-related macular degeneration (AMD) [ 11 – 13 ], but retinal inflammation after radiation has scarcely been explored, although clinical observations suggest that anti-inflammatory drugs such as corticosteroids may reduce RR manifestations [ 14 ]. In addition, the time course of glial and inflammatory cell activation has not been fully described, despite leukostasis being identified as an early pathogenic event [ 15 ], and whether retinal inflammation contributes to the microvascular damage occurring in RR remains uncertain.…”

Alpha-Melanocyte-Stimulating Hormone Maintains Retinal Homeostasis after Ischemia/Reperfusion

“…The IRI results in elevated levels of reactive oxygen species that mediate tissue damage and apoptosis associated with permanent vision impairment and blindness. There is a potential role of immune cells with retinal cell loss in that retinal IRI sequesters CD4+ T cells and macrophages in the retina, facilitating the degeneration of retinal ganglion cells (RGCs) [3,9]. Therapeutic injections of T-cell-blocking antibodies attenuated RGC and retina function in an experimental retinal IRI model.…”