PURPOSE: Increasing evidence supports a role for complement in the pathogenesis of @entity1020 ( @entity1020 ). This study evaluated retinal microglia, T-lymphocytes, and complement deposition in a light-induced @entity989 model. The effect of a @entity750 ( @entity750 , @entity750 (1A)) agonist on these processes was investigated. METHODS: @entity35 were dark adapted for 24 hours before a 6-hour blue light exposure. Some animals were predosed subcutaneously with AL-8309A. Retinas were evaluated at different times after light exposure. @entity982 sections were stained with antibody for a microglial marker ( @entity16339 ), a T-lymphocyte marker (CD3), and complement components C1q, C3, factor B, factor H, and membrane attack complex (MAC). RESULTS: Light exposure resulted in substantial photoreceptor and RPE loss. Robust microglia activation and migration to the outer retina occurred rapidly. Substantial T-lymphocyte recruitment did not occur. Complement alternative pathway was strongly activated, resulting in the deposition of C3, factor B, factor H, and MAC in the area of photic lesions. Dosing with AL-8309A prevented @entity989 and decreased microglia activation/recruitment and complement deposition in the outer retina. CONCLUSIONS: In blue light exposed retinas, microglia were activated and migrated toward the outer retina, whereas a T-lymphocyte response was minimal. The innate immune system was markedly activated, with substantial complement deposition in the outer retina after light exposure. This complement deposition was prevented by AL-8309A. This model may be useful in the evaluation of complement inhibitors and other neuroprotectants intended for ocular use. AL-8309 is under evaluation in the clinic and may be useful in the treatment of @entity1020 .

Complement deposition and microglial activation in the outer retina in light-induced XXXX : inhibition by a 5-HT1A agonist.

@entity16339 :: ('29427(Tax:10116)', 'Gene') :: ['Iba1'] @entity982 :: ('MESH:D010232', 'Chemical') :: ['Paraffin'] @entity750 :: ('MESH:D012701', 'Chemical') :: ['5-hydroxytryptamine', 'serotonin', '5-HT'] @entity989 :: ('MESH:D012164', 'Disease') :: ['retinal lesions', 'retinopathy'] @entity35 :: ('10116', 'Species') :: ['Rats'] @entity1020 :: ('MESH:D008268', 'Disease') :: ['AMD', 'age-related macular degeneration']
@entity989 :: (MESH:D012164,Disease) :: ['retinopathy']
