Disruption of retinal inflammation and the development of diabetic retinopathy in mice by a CD40-derived peptide or mutation of CD40 in Muller cells.

ABSTRACT:

Aims/hypothesis

CD40 expressed in Müller cells is a central driver of diabetic retinopathy. CD40 causes phospholipase Cγ1 (PLCγ1)-dependent ATP release in Müller cells followed by purinergic receptor (P2X₇)-dependent production of proinflammatory cytokines in myeloid cells. In the diabetic retina, CD40 and P2X₇ upregulate a broad range of inflammatory molecules that promote development of diabetic retinopathy. The molecular event downstream of CD40 that activates the PLCγ1-ATP-P2X₇-proinflammatory cytokine cascade and promotes development of diabetic retinopathy is unknown. We hypothesise that disruption of the CD40-driven molecular events that trigger this cascade prevents/treats diabetic retinopathy in mice.

Methods

B6 and transgenic mice w

SUBMITTER: Portillo JC 

PROVIDER: S-EPMC9630214 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature