PURPOSE: Photoreceptor apoptosis and resultant @entity227 occur in @entity1 and animalswith inherited, and disease-, injury- and chemical-induced @entity2000 . Our aims were three-fold: 1) to determine the kinetics of rod apoptosis and @entity141 overload in Pde6brd1 @entity19 and developmentally lead-exposed @entity35 , 2) to establish a pathophysiologically- relevant model of @entity141 overload/rod-selective apoptosis in isolated @entity35 retina and 3) to examine different mechanistic based neuroprotective strategies that would abrogate or mollify rod @entity141 overload/apoptosis. METHODS: Retinal morphometry and elemental @entity460 content ([ @entity9495 ]) determined the kinetics of rod apoptosis and @entity141 overload. A multiparametric analysis of apoptosis including rod [ @entity9495 ], a live/dead assay, rod @entity26 consumption, cytochrome c immunoblots and caspase assays was combined with pharmacological studies of an isolated @entity35 retinal model of rod-selective @entity141 overload/apoptosis. RESULTS: @entity141 overload preceded rod apoptosis in @entity19 and @entity35 , although the extent and kinetics in each differed significantly. The isolated @entity35 model of rod @entity141 overload/apoptosis showed that blockade of @entity141 entry through rod @entity6708 -activated channels with L-cis @entity3988 was partially neuroprotective, whereas blockade of @entity141 entry into rods through L-type @entity141 channels with D-cis @entity3988 or @entity1855 provided no protection. Inhibition of the mitochondrial @entity4024 / @entity141 exchanger with D-cis @entity3988 provided no protection. @entity9472 and @entity20200 , mitochondrial permeability transition pore (mPTP) inhibitors, blocked all @entity141 - induced apoptosis, whereas the @entity4124 inhibitor DEVD-fmk only blocked the downstream cytochrome c-induced apoptosis. CONCLUSIONS: The successful pharmacological neuroprotective strategies for rod @entity141 overload/ apoptosis targeted the rod @entity6708 -activated channels or mPTP, but not the rod L-type @entity141 channels. Eur J Ophthalmol 2003; 13 (Suppl. 3): S 44-S56.

Pharmacological strategies to block rod photoreceptor apoptosis caused by XXXX overload: A mechanistic target-site approach to neuroprotection.

@entity1 :: ('9606', 'Species') :: ['humans'] @entity6708 :: ('CHEBI:16356', 'Chemical') :: ['cGMP'] @entity2000 :: ('MESH:D012162', 'Disease') :: ['retinal degeneration'] @entity227 :: ('MESH:D014786', 'Disease') :: ['visual deficits'] @entity4024 :: ('D012964', 'Chemical') :: ['Na+'] @entity9472 :: ('D016572', 'Chemical') :: ['CsA'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity1855 :: ('MESH:D014700', 'Chemical') :: ['verapamil'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity20200 :: ('MESH:C090438', 'Chemical') :: ['NIM811'] @entity3988 :: ('MESH:D004110', 'Chemical') :: ['diltiazem'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity4124 :: ('25402(Tax:10116)', 'Gene') :: ['caspase-3'] @entity9495 :: ('D002118', 'Chemical') :: ['Ca']
@entity460 :: (MESH:D002118,Chemical) :: ['calcium']
