Non-invasive occular biomarkers for early diagnosis of diseases
View Patent ↗Materials and methods are disclosed for screening advanced glycation end-products from the mammalian ocular lens proteins to quantify early biomarkers for the diagnosis of diabetes mellitus and related complications.
1. A method for diagnosing a disease or condition in a subject at an early stage to facilitate treatment by screening of the ocular lens of the subject at 435 nm, wherein the method comprises:
(a) detecting an advanced glycation end-product fluorophores that formed in the α-crystallin of the ocular lens and surrounding tissue, using steady state and time resolved fluorescence in a sequential order and recording results;
(b) quantifying the fluorophores formed on the α-crystallin to determine the fluorescence lifetimes of the fluorophores;
(c) using the fluorescence lifetimes to distinguish between normal and pathological ocular lens and surrounding tissue; and
(d) diagnosing the disease based on the presence of pathological ocular lens lifetimes in the subject.
2. The method of claim 1 wherein the disease or condition is diabetes or diabetic retinopathy.
3. The method of claim 1 , wherein spectroscopic changes in the visible spectrum between 401-600 nm are based on fluorescence lifetimes with aging and pathological conditions in a small heat shock protein, α-crystallin and its subunits.
4. The method for diagnosing a disease or condition of claim 1 , further defined as analyzing aging and pathological conditions in the eye.
5. The method of claim 1 , wherein the fluorophores are advanced glycation endproducts (AGEs) when measured in vitro from the lens tissue sample and wherein in vivo, the fluorophores are a combination of advanced glycation end products formed on macromolecules in the eye.
6. The method of claim 5 wherein other fluorophores further are selected from the group consisting of A2E, lipofuscin, FAD and NADH.
7. The method of claim 1 , wherein the disease diagnosed by screening the lens is based on quantifying two or more fluorescence lifetimes in the range of 1.6 to 17 ns.
8. The method of claim 1 , wherein fluorophores in the eye are used for differential diagnosis.