Method for the identification of agents that inhibit or promote cataracts and uses thereof
AssigneeThe General Hospital Corporation
InventorsLee E. Goldstein, Ashley I. Bush
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Abstract
Described are methods for the identification of agents useful in the treatment or prevention of cataracts. Also described are methods for the identification of agents that may inadvertently promote or accelerate the formation of cataracts, and methods of treating or preventing injuries to or diseases of the ocular lens, retina and/or macula. More specifically, the invention describes methods for the identification of pharmacological agents useful in treating cataracts by inhibiting the cross-linking of eye lens proteins.
Claims22
A method for the identification of a candidate pharmacological agent that results in the prevention of or reduction in cross-linking of a target protein, said method comprising:
- (a) adding a reducible redox-active metal source to a first sample of the target protein comprising an auto-oxidizing kynurenine pathway metabolite;
- (b) allowing said first sample to incubate for an amount of time sufficient to allow cross-linking of said target protein;
- (c) adding said reducible redox-active metal source to a second sample of the target protein comprising an auto-oxidizing kynurenine pathway metabolite, said second sample additionally comprising a candidate pharmacological agent;
- (d) allowing said second sample to incubate for the same amount of time as said first sample;
- (e) determining the amount of target protein cross-linking by said first sample and said second sample;
- and
- (f) comparing the amount of target protein cross-linking produced by said first sample to the amount of target protein cross-linking produced by said second sample;
- whereby a decrease in the amount of target protein cross-linking produced by said second sample, as compared to said first sample, indicates that said candidate pharmacological agent is useful in the treatment of cataracts.
An assay method for determining whether a candidate agent causes or accelerates the cross-linking of a target protein, wherein an increase in target protein cross-linking indicates potential cataract formation, said method comprising:
- (a) adding a reducible redox-active metal source to a first sample of the target protein comprising an auto-oxidizing kynurenine pathway metabolite;
- (b) allowing said first sample to incubate for an amount of time sufficient to allow cross-linking of said target protein;
- (c) adding said reducible redox-active metal source to a second sample of the target protein comprising an auto-oxidizing kynurenine pathway metabolite, said second sample additionally comprising a candidate agent;
- (d) allowing said second sample to incubate for the same amount of time as said first sample;
- (e) determining the amount of target protein cross-linking by said first sample and said second sample;
- and
- (f) comparing the amount of target protein cross-linking produced by said first sample to the amount of target protein cross-linking produced by said second sample;
- whereby an increase in the amount of target protein cross-linking produced by said second sample, as compared to said first sample, indicates that said agent may cause or accelerate the formation of cataracts.
Dependencies are inferred from the claim text.