Current hypotheses for the biochemical basis of diabetic retinopathy.
Diabetic retinopathy is one of the leading causes of vision loss in industrialized countries. Despite recent advances, the biochemical basis for the development of this diabetic complication is uncertain. Although retinal circulation is unique in that it is readily observable noninvasively, retinal tissue is extremely difficult to study in humans because of the problems inherent in obtaining fresh, appropriate biopsy material. Moreover, because of the difficulties in working with animal models of diabetic retinopathy, such as the dog, many investigators have turned to cell-culture models, especially those using primary cultures of retinal capillary endothelial cells and pericytes. Diabetic retinopathy involves both morphological and functional changes in the retinal capillaries. Morphological changes include basement membrane thickening and pericyte disappearance; functional changes include one important early change--increased permeability--which may be attributable to endothelial cell changes and basement membrane leakiness. Investigators have described major biochemical changes in cellular signaling pathways, including myo-inositol, inositol phosphates, and DAG metabolism, as well as decreased Na(+)-K(+)-ATPase and increased PKC activity. These defects may be related to the way endothelial cells and pericytes synthesize and interact with the extracellular matrix. Abnormalities in endothelial cell or pericyte interaction with the basement membrane may in turn lead to functional abnormalities, such as increased permeability.
Mandarino
L J
LJ
Department of Ophthalmology, Eye & Ear Institute of Pittsburgh, PA 15213.
D001485:Basement Membrane / Q000473:pathology; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D012171:Retinal Vessels / Q000473:pathology / Q000503:physiopathology; D013012:Sorbitol / Q000378:metabolism; D014652:Vascular Diseases / Q000503:physiopathology
D013012:Sorbitol; D005947:Glucose