Fractalkine ( @entity20598 or FKN) is a membrane-bound chemokine expressed on neuronal membranes and is proteolytically cleaved to shed a soluble chemoattractant domain. FKN signals via its unique receptor @entity21846 expressed on microglia and other peripheral leukocytes. The aim of this study is to determine the role of @entity21846 in inflammatory-mediated damage to retinal neurons using a model of @entity6 . For this, we compared neuronal, microglial, and astroglial densities and inflammatory response in nondiabetic and @entity6 ( @entity15979 (Akita)) @entity21846 -wild-type and @entity21846 -deficient @entity19 at 10 and 20 weeks of age. Our results show that @entity15979 (Akita) @entity21846 -knockout @entity19 exhibited (a) decreased neuronal cell counts in the retinal ganglion cell layer, (b) increased microglial cell numbers, and (c) decreased astrocyte responses comparable with @entity15979 (Akita) @entity21846 -Wild-type @entity19 at 20 weeks of age. Analyses of the inflammatory response using PCR arrays showed several inflammatory genes differentially regulated in @entity6 tissues. From those, the response in @entity15979 (Akita) @entity21846 -deficient @entity19 at 10 weeks of age revealed a significant upregulation of @entity635 at the transcript level that was confirmed by enzyme-linked immunosorbent assay in soluble retinal extracts. Overall, @entity635 , @entity1611 , and @entity3542 levels as a read out of @entity842 production were abundant in @entity15979 (Akita) @entity21846 -deficient retina. Notably, double immunofluorescence staining shows that astrocytes act as a source of @entity635 in the @entity15979 (Akita) retina, and @entity21846 -deficient microglia potentiate the inflammatory response via @entity635 release. Collectively, these data demonstrate that dysregulated microglial responses in absence of @entity21846 contribute to inflammatory-mediated damage of neurons in the @entity6 .

Disruption of Fractalkine Signaling Leads to Microglial Activation and Neuronal Damage in the XXXX Retina.

@entity6 :: ('MESH:D003920', 'Disease') :: ['diabetic', 'diabetic retina', 'diabetic retinopathy'] @entity20598 :: ('20312(Tax:10090)', 'Gene') :: ['CX3CL1'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity635 :: ('16176(Tax:10090)', 'Gene') :: ['IL-1b'] @entity3542 :: ('CHEBI:16301', 'Chemical') :: ['nitrite'] @entity21846 :: ('13051(Tax:10090)', 'Gene') :: ['CX3CR1'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity1611 :: ('22339(Tax:10090)', 'Gene') :: ['VEGF'] @entity15979 :: ('16334(Tax:10090)', 'Gene') :: ['Ins2']
@entity6 :: (MESH:D003920,Disease) :: ['Diabetic']
