Microglia-Müller Glia Crosstalk in the rd10 Mouse Model of Retinitis Pigmentosa

Abstract

Retinitis pigmentosa refers to a large, genetically heterogeneous group of retinal dystrophies. This condition is characterized by the gradual onset of blindness due to progressive deterioration of the retina, a process that includes photoreceptor and retinal-pigmented-epithelium cell decay and death, microglial recruitment, reactive gliosis, and vascular disorganization and regression. We found that early in the degenerative process, the rd10 mouse retina exhibits high levels of photoreceptor cell death and reactive Müller gliosis. In explant cultures, both degenerative processes were abrogated by IGF-I treatment. Moreover, the beneficial effect of IGF-I was diminished by microglial depletion using clodronate-containing liposomes. Interestingly, in the absence of IGF-I, microglial depletion partially prevented cell death without affecting Müller gliosis. These findings strongly suggest a role for microglia-Müller glia crosstalk in neuroprotection. However, a subpopulation of microglial cells appears to promote neurodegeneration in the dystrophic retina. Our findings indicate that beneficial neuroprotective effects may be achieved through strategies that modulate microglial cell responses.

Glia–neuron interactions in the mammalian retina

“…Chemical destruction of microglia in rd10 mouse retinal explants with clodronatecontaining liposomes slowed photoreceptor death, yet the neuroprotective effect of IGF-I was attenuated when microglia were depleted. These findings suggest a misbalance in the microglial neuroprotective/neurotoxic intervention in this retinal dystrophy (Arroba et al, 2011(Arroba et al, , 2014. In a rat model of RP bearing a mutation in the rhodopsin-encoding gene (P23H), microglial cells were more abundant in all retinal layers and they were also present in the subretinal space.…”

Heterogeneous astrocytes: Active players in CNS

“…Activated microglia is shown to control the rate of astrocyte proliferation and prevent astrogliosis by releasing NO (Quintas et al 2014). In rat retinitis pigmentosa model, microglia-Mϋller glia crosstalk exerts the neuroprotective effects in CNS diseases (Arroba et al 2014). Moreover, the interaction between astrocytes and microglia also contributes to the potential pathogenesis of many CNS disorders (Gao et al 2013;Saijo et al 2009;von Bernhardi and Ramirez 2001).…”

Purinergic signaling in retinal degeneration and regeneration

“…Upregulation of TNFa, IL-1b, and IL-6 may be involved in the death of retinal ganglion cells that occurs with P2X 7 activation after elevation of the intraocular pressure . Suppression of microglia activation or depletion of microglial cells have protective effects in models of various retinopathies like, for example, hereditary and light-induced photoreceptor degeneration, and diabetic retinopathy Liu et al, 2012;Peng et al, 2014;Zeng et al, 2014;Arroba et al, 2014). ATP and ADP released from damaged neurons and activated macroglial cells contribute to microglia activation in the retina.…”