Muller glia in retinal innate immunity: a perspective on their roles in endophthalmitis

Abstract

Muller cells are the predominant glial cell type in the retina and have a unique anatomy, with processes that span the entire retinal thickness. Although extensive morphological and physiological studies of Muller glia have been performed, much less is known about their role in retinal innate immunity, specifically in infectious endophthalmitis. They were found to express toll-like receptors (TLRs), a major family of pattern recognition receptors that mediate innate responses and provide an important mechanism by which Muller glia are able to sense both pathogen- and host-derived ligands in the vitreous and the retina. An increasing body of evidence suggests that TLR-signaling mediates beneficial effects in the retina via production of proinflammatory cytokines/chemokines, antimicrobial peptides, and neuroprotective growth factors to restore tissue homeostasis. In this review, we discussed retinal innate immunity in general with emphasis on the role of Muller glia in initiating retinal innate defense.

Fig 1. Pathogenesis of bacterial endophthalmitis

The entry of bacteria into the eye occurs due to breakdown of the ocular barriers during intraocular surgery or postsurgical complications. Once inside the vitreous cavity, retinal residential cells i.e. microglia, Muller, astrocytes and RPE recognize the invading pathogen via pathogen recognizing receptors (PRRs, e.g. TLRs). These TLR-activated retinal cells initiate the cascade of innate response involving the production of proinflammatory cytokines/chemokines. The infiltrating monocytes and neutrophils further add to the pro-inflammatory signal by secreting more cytokines into the vitreous which culminates into irreversible retinal damage and subsequent loss of vision.

Fig.2. Pleiotropic roles of Muller glia in retinal innate defense

Following microbial invasion, Muller cells get activated via TLRs or other innate immune receptor-signaling leading to the production of pro-inflammatory cytokines chemokines and antimicrobial peptides. These inflammatory mediators drive the recruitment of PMNs and other innate immune cells to the retina. These early innate responses incited by infection plays an important role in bacterial clearance; however, its dysregulation can lead to bystander damage to retinal neurons. To counter these effects Muller also produces neurotrophins (NTs) which provided neuroprotection via binding their receptors expressed on the retinal neurons, neuron e.g. ganglion cells or photoreceptors.