AIMS/HYPOTHESIS: Glycated proteins, formed by reaction of glucose and protein, react further yielding numerous, mostly undefined advanced glycation end products (AGE). The recently characterized imidazolone-type AGE (AG-1) is non-oxidatively formed involving 3-deoxyglucosone whereas some AGEs, particularly N(epsilon)-(carboxymethyl)lysine (CML), are formed only in the presence of oxygen. METHODS: To study the possible contribution of oxidative and non-oxidative AGE formation in the development of diabetic retinopathy antibodies directed against CML-type and imidazolone-type AGEs were characterized by dot blot analysis and used to localize these well-characterized epitops in the retinas from diabetic rats (early course) and from human Type I (insulin-dependent) diabetes mellitus with laser-treated proliferative diabetic retinopathy (late course). RESULTS: In non-diabetic rats CML was moderately positive in neuroglial and vascular structures of non-diabetic rat retinas and increased strongly in diabetic retinas. Anti-imidiazolone antibody staining was strongly positive only in diabetic capillaries. Advanced human diabetic retinopathy showed strong CML-immunolabelling of the entire retina whereas control samples showed moderate staining of neuroglial structures only with the polyclonal CML-antibody. Anti-imidiazolone antibody staining was faint in the inner retina of control sections but were strong throughout the entire diabetic retina. Immunolabelling for the AGE-receptor was congruent with a marker of Müller cells. CONCLUSION/ INTERPRETATION: Our data indicate that the oxidatively formed CML is present in non-diabetic retinas as a regular constituent but increases in diabetes both in neuroglial and vascular components. Imidazolone-type AGE are restricted to microvessels and spread during later stages over the entire retina, co-localizing with the expression of AGE-receptor.
AIMS/HYPOTHESIS: Glycated proteins, formed by reaction of glucose and protein, react further yielding numerous, mostly undefined advanced glycation end products (AGE). The recently characterized imidazolone-type AGE (AG-1) is non-oxidatively formed involving 3-deoxyglucosone whereas some AGEs, particularly N(epsilon)-(carboxymethyl)lysine (CML), are formed only in the presence of oxygen. METHODS: To study the possible contribution of oxidative and non-oxidative AGE formation in the development of diabetic retinopathy antibodies directed against CML-type and imidazolone-type AGEs were characterized by dot blot analysis and used to localize these well-characterized epitops in the retinas from diabeticrats (early course) and from humanType I (insulin-dependent) diabetes mellitus with laser-treated proliferative diabetic retinopathy (late course). RESULTS: In non-diabeticratsCML was moderately positive in neuroglial and vascular structures of non-diabeticrat retinas and increased strongly in diabetic retinas. Anti-imidiazolone antibody staining was strongly positive only in diabetic capillaries. Advanced humandiabetic retinopathy showed strong CML-immunolabelling of the entire retina whereas control samples showed moderate staining of neuroglial structures only with the polyclonal CML-antibody. Anti-imidiazolone antibody staining was faint in the inner retina of control sections but were strong throughout the entire diabetic retina. Immunolabelling for the AGE-receptor was congruent with a marker of Müller cells. CONCLUSION/ INTERPRETATION: Our data indicate that the oxidatively formed CML is present in non-diabetic retinas as a regular constituent but increases in diabetes both in neuroglial and vascular components. Imidazolone-type AGE are restricted to microvessels and spread during later stages over the entire retina, co-localizing with the expression of AGE-receptor.
Authors: Aaron J Fields; Britta Berg-Johansen; Lionel N Metz; Stephanie Miller; Brandan La; Ellen C Liebenberg; Dezba G Coughlin; James L Graham; Kimber L Stanhope; Peter J Havel; Jeffrey C Lotz Journal: J Orthop Res Date: 2015-03-02 Impact factor: 3.494
Authors: A Lecleire-Collet; L H Tessier; P Massin; V Forster; G Brasseur; J A Sahel; S Picaud Journal: Br J Ophthalmol Date: 2005-12 Impact factor: 4.638
Authors: Gözde Hondur; Emre Göktas; Xiangjun Yang; Lama Al-Aswad; James D Auran; Dana M Blumberg; George A Cioffi; Jeffrey M Liebmann; Leejee H Suh; Danielle Trief; Gülgün Tezel Journal: Invest Ophthalmol Vis Sci Date: 2017-08-01 Impact factor: 4.799