Figure 3.

Microglia are important in the post-natal maturation of cone photoreceptors. (A) Microglia make contact with photoreceptor synapses as shown in the electron micrograph, with Cx3cr1-EGFP-labeled microglial processes (black deposit, circled in red) in close proximity to photoreceptor ribbons (asterisk, *), within the synapse (outlined in blue). (B) Microglia (green; Iba-1) are also observed to contact multiple cone photoreceptors (red; peanut agglutinin, PNA) within the outer retina. (C) During cone photoreceptor postnatal development, function is reduced in Cx3cr1null animals from around P14 (electroretinogram, black squares), while cones are lost from 1 month of age (PNA quantification, red squares). *p < 0.05, ****p < 0.0001. (D) During outer segment elongation which occurs after eye opening (>P14) there is a reduced length of centrin (black squares) and Rpgrip1 (red squares) expression within the cone photoreceptor cilium of the Cx3cr1null mice compared to wildtypes (circles). (E) A schematic showing that microglial communication with cone photoreceptors via the receptor Cx3cr1 is important in postnatal maturation, with loss of this receptor (Cx3cr1null) leading to restricted expression of key cilium proteins during eye opening, reduced outer segment elongation, dysfunction and ultimately cell death (Jobling et al., 2018b).