Vitreous fluid of db/db mice exhibits alterations in angiogenic and metabolic factors consistent with early diabetic retinopathy.
BACKGROUND
This study evaluated the postulate that the vitreous of diabetic db/db mice, a genetic model of type 2 diabetes that manifests hyperglycemia and insulin resistance, exhibits alterations in angiogenic and metabolic factors that reflect abnormalities in the retinal microvasculature participatory in the pathogenesis of diabetic retinopathy.


METHODS
Vitreous obtained from db/db and age-matched nondiabetic db/m mice was analyzed by Western blot for pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF), by immunoassay for type IV collagen, and by measurement of TBARs for lipid peroxide products.


RESULTS
Compared to nondiabetic db/m controls, vitreous from db/db mice contained decreased PEDF and increased VEGF (VEGF:PEDF relative ratio 2.2 +/- 0.3 and 1.0 +/- 0.1 in db/db vs. db/m, respectively; p < 0.05), and elevated concentrations of lipid peroxide products (187 +/- 43 and 84 +/- 15 ng/ml in db/db vs. db/m, respectively; p < 0.05) and type IV collagen (5.2 +/- 0.7 and 3.1 +/- 0.4 nmol/ml in db/db vs. db/m, respectively; p < 0.05). These changes were observed at age 18-20 weeks, consistent with an early stage in the development of retinal microvascular pathology.


CONCLUSIONS
The findings support the potential usefulness of vitreous from the db/db mouse as a model tissue for investigation of pathogenetic factors and assessment of therapeutic interventions in early diabetic retinopathy.
Cohen
Margo P
MP
Glycadia, Inc., Philadelphia, PA, USA. drmpcohen@aol.com
Hud
Elizabeth
E
Shea
Elizabeth
E
Shearman
Clyde W
CW
D043924:Angiogenesis Modulating Agents / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D024141:Collagen Type IV / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004195:Disease Models, Animal; D005136:Eye Proteins; D007118:Immunoassay; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors; D009994:Osmolar Concentration; D015843:Serpins; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D014822:Vitreous Body / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D043924:Angiogenesis Modulating Agents; D024141:Collagen Type IV; D005136:Eye Proteins; D008054:Lipid Peroxides; D009414:Nerve Growth Factors; D015843:Serpins; D017392:Thiobarbituric Acid Reactive Substances; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor