Figure 8. Activation and self-perpetuation of the response of local immune competent cells in diabetic retinopathy.

Diabetes activates immune competent cells including micro- and macroglia (astrocytes and Müller glial cells) via multiple mechanisms, potentially inducing a self-perpeutating and amplification loop. Diabetes can directly induce activation of quiescent microglia (orange) leading to increase in number, change in morphology, and increased production of pro-inflammatory mediators. Similarly, diabetes also induces macroglia (green) to undergo activation and result in increased production of pro-inflammatory mediators. Finally, endothelial cells and neurons (pink) can also respond to diabetes by producing pro-inflammatory mediators. Any and all of these responses participate in the shift from immune-privileged to a highly pro-inflammatory ocular environment, and amplifies the activation of micro-and macroglia in an autocrine, and paracrine fashion. Once set in motion, this creates a loop in which de-activation of these immune competent cells is rendered highly difficult even when the trigger (i.e. suboptimal controlled diabetes) has been “removed”.