Biomarkers Useful in the Treatment of Subjects Having Disease of the Eye
AssigneeThe Johns Hopkins University
InventorsPeter A. Campochiaro, Lili LU, Craig S. Rosenfeld
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Abstract
The present invention provides biomarkers of oxidative stress in subjects with retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, Fuchs' dystrophy, diabetic macular edema (DME), geographic atrophy, Stargardt's disease, or retinal vein occlusion (RVO), and their use in identifying subjects in need of treatment and methods for staging the severity of the disease.
Claims22
A method for quantifying or staging the severity of an eye disease associated with oxidative stress comprising:
- a) obtaining a biological sample from the subject;
- b) providing a control biological sample;
- c) measuring one or more of the following:
- cupric reducing antioxidant capacity, GSH/GSSG ratio, and carbonyl adduct level in the sample of a) and b);
- d) comparing the one or more measurements of c) in the sample from the subject to the control sample;
- and
- e) quantifying or staging the severity of disease in the subject as progressing in stage, or increasing in severity, if the levels of cupric reducing antioxidant capacity and/or GSH/GSSG ratio is reduced relative to the control sample, and/or if the levels of carbonyl adduct level is elevated relative to the control sample.
A method for treating a subject having a disease selected from retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, or Fuchs' dystrophy comprising:
- a) obtaining a biological sample from the subject;
- b) providing a control biological sample;
- c) measuring one or more of the following:
- cupric reducing antioxidant capacity, GSH/GSSG ratio, carbonyl adduct level in the sample of a) and b);
- d) comparing the one or more measurements of c) in the sample from the subject to the control sample;
- e) quantifying or staging the severity of the disease in the subject as progressing in stage, or increasing in severity, if the levels of cupric reducing antioxidant capacity and/or GSH/GSSG ratio is reduced relative to the
- f) control sample, and/or if the levels of carbonyl adduct level is elevated relative to the control sample;
- and
- g) selecting a course of treatment for the disease in the subject which is based on the stage or severity of disease indicated in e).
A method for monitoring the treatment of a subject having retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, myopia, high myopia, Fuchs' dystrophy, diabetic macular edema (DME), geographic atrophy, Stargardt's disease, or retinal vein occlusion (RVO) comprising:
- a) obtaining a biological sample from the subject;
- b) providing a control biological sample;
- c) measuring one or more of the following:
- cupric reducing antioxidant capacity, GSH/GSSG ratio, carbonyl adduct level, in the sample of a) and b);
- d) comparing the one or more measurements of c) in the sample from the subject to the control sample;
- e) determining the stage or the severity of disease in the subject, wherein if the levels of cupric reducing antioxidant capacity and/or GSH/GSSG ratio is reduced relative to the control sample, and/or if the levels of carbonyl adduct level is elevated relative to the control sample then the disease is identified as progressing in stage, or increasing in severity, or if the levels of cupric reducing antioxidant capacity and/or GSH/GSSG ratio is elevated relative to the control sample and/or if the levels of carbonyl adduct level is reduced relative to the control sample then the disease is identified as reducing in stage, or decreasing in severity of the retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, or Fuchs' dystrophy;
- f) selecting a course of treatment for the disease in the subject which is based on the stage or severity of disease indicated in e);
- and
- g) after administration of the course of treatment to the subject, repeating steps one or more times.
A method for quantifying oxidative stress comprising:
- a) obtaining a biological sample from the subject;
- b) providing a control biological sample;
- c) measuring one or more of the following:
- cupric reducing antioxidant capacity, GSH/GSSG ratio, and carbonyl adduct level in the sample of a) and b);
- and
- d) comparing the one or more measurements of c) in the sample from the subject to the control sample, wherein an increase in carbonyl adduct level, a ratio of GSH to GSSG is reduced, and/or a reduction in cupric antioxidant capacity is indicative of oxidative stress.
A kit for determining the oxidative stress of the eye comprising:
- a) a first container for a biological sample from the subject;
- b) a second container for a control biological sample;
- c) one or more vials that comprise reagents to determine:
- cupric reducing antioxidant capacity, GSH/GSSG ratio, and carbonyl adduct level in the sample of a) and b);
- and
- d) instructions for comparing the one or more measurements of c) in the sample from the subject to the control sample, wherein an increase in carbonyl adduct level, a ratio of GSH to GSSG is reduced, and/or a reduction in cupric antioxidant capacity is indicative of oxidative stress.
Dependencies are inferred from the claim text.