AIMS/HYPOTHESIS: Retinal M  ller cells are known to produce inflammatory and angiogenic cytokines, which play important roles in @entity6 . @entity519 -inducible factor (HIF)-1 has been shown to play a crucial role in retinal @entity32 and neovascularisation. We sought to determine the role of M  ller cell-derived HIF-1 in @entity26 -induced @entity989 (OIR) and @entity6 using conditional @entity1965 (also known as @entity1965 ) knockout (KO) @entity19 . METHODS: Conditional @entity1965 KO @entity19 were generated by crossing @entity19 expressing cyclisation recombinase (cre, also known as P1_gp003) in M  ller cells with floxed @entity1965 @entity19 and used for OIR and @entity3839 -induced @entity6 to induce @entity2479 and @entity32 , respectively. Abundance of @entity1965 and pro-angiogenic and pro-inflammatory factors was measured by immunoblotting and immunohistochemistry. @entity2479 was visualised by angiography and quantified by counting pre-retinal nuclei. Retinal @entity32 was evaluated by @entity455 . RESULTS: While the @entity1965 KO @entity19 showed significantly decreased @entity1965 levels in the retina, they exhibited no apparent histological or @entity227 under normal conditions. Compared with wild-type counterparts, @entity1965 KO @entity19 with OIR demonstrated attenuated overproduction of @entity1611 ( @entity1611 ) and @entity8024 , reduced vascular leakage and alleviated neovascularisation in the retina. Under @entity6 conditions, disruption of @entity1965 in M  ller cells attenuated the increases of @entity989 and adherent leucocytes, as well as the overproduction of @entity1611 and @entity8024 . CONCLUSIONS/INTERPRETATION: M  ller cell-derived @entity1965 is a key mediator of @entity2479 , vascular leakage and @entity32 , the major pathological changes in @entity6 . M  ller cell-derived @entity1965 is therefore a promising therapeutic target for @entity6 .

Ischaemia-induced @entity2479 and XXXX in @entity19 with conditional knockout of @entity519 -inducible factor-1 in retinal M  ller cells.

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity227 :: ('MESH:D014786', 'Disease') :: ['visual functional abnormalities'] @entity455 :: ('MESH:D014652', 'Disease') :: ['leucostasis and vascular leakage'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes', 'diabetic retinopathy'] @entity2479 :: ('MESH:D012173', 'Disease') :: ['retinal neovascularisation', 'Retinal neovascularisation'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity3839 :: ('MESH:D013311', 'Chemical') :: ['streptozotocin'] @entity519 :: ('MESH:D000860', 'Disease') :: ['Hypoxia'] @entity8024 :: ('15894(Tax:10090)', 'Gene') :: ['ICAM-1', 'intercellular adhesion molecule (ICAM)-1'] @entity1965 :: ('15251(Tax:10090)', 'Gene') :: ['HIF-1a', 'Hif-1a', 'Hif1a'] @entity989 :: ('MESH:D012164', 'Disease') :: ['retinopathy', 'retinal vascular leakage'] @entity1611 :: ('22339(Tax:10090)', 'Gene') :: ['vascular endothelial growth factor', 'VEGF']
@entity6 :: (MESH:D003920,Disease) :: ['diabetic retinopathy']
