Abstract
Purpose: :
The aim of this study is to analyze common changes in the molecular composition of basement membranes (BM) in diabetic retina and kidney. In the retina, they occur in the Bruch’s membrane, the inner limiting membrane (ILM) and as capillary BMs forming part of the blood-retina barrier. In the kidney, they are found in the capillaries, Bowman’s capsule and renal tubules. BMs are primarily composed of laminins, nidogens, collagen IV, and perlecan. While BM thickening in diabetic retinopathy and nephropathy is a general observation, there is no knowledge of the molecular basis of this phenomenon.
Methods: :
C57B1/6J mice were rendered diabetic (defined by blood glucose > 300 mg/dl) with five consecutive intraperitoneal injections of STZ (65mg/kg) daily. After a survival period of 2, 4 or 6 months, eyes and kidneys were excised and examined by histological and immunohistochemical techniques. We used a panel of antibodies against laminins, nidogens, collagen IV, and perlecan to describe the composition of the normal and diabetic retinal and renal BMs. We also compared the size and the wet weight between normal and diabetic kidneys.
Results: :
Compared to the controls, there was no difference for the laminin-1 and perlecan immunoreactivity in both diabetic kidneys and diabetic retinae. Immunoreactivity for nidogen-1 (normally highly expressed in all BM) and nidogen-2 (normally moderately expressed in all BM) appeared to increase in both diabetic retinae and kidneys. There was an increase in collagen IV immunoreactivity in the glomerular and proximal tubular BMs; but such increase was not observed in the diabetic retinae. On the contrary, Immunoreactivity for the laminin α4 chain (containing in laminin-8, -9 and -14) was enhanced in the capillaries of the diabetic retinae, while immunoreactivitiy for this BM component was weak in both the control and the diabetic kidneys.
Conclusions: :
These data suggest that some BM components are up-regulated in both diabetic retinopathy and nephropahty (e.g. nidogen-1 and -2). More importantly, we found differential up-regulation of collagen IV and laminin α4 chain in diabetic nephropathy and diabetic retinopathy, respectively. Such difference may shed light on the different molecular changes in the diabetic kidney and retina.
Keywords: diabetic retinopathy