Early biosynthetic changes in the diabetic-like retinopathy of galactose-fed rats.
The histological lesions of diabetic micro-angiopathy have a long latency, but vascular cell function may be affected at early stages of the process. Rats with experimental galactosaemia develop a diabetic-like retinopathy in the absence of other metabolic abnormalities characteristic of diabetes mellitus; basement membrane thickening is measurable in their retinal vessels after 7 months of galactose feeding. To examine the course of biosynthetic changes relevant to the process, retinal expression of collagen IV and fibronectin were compared in rats fed a 30% galactose diet or a control diet for 5 or 9 weeks. Total retinal RNA was studied by reverse transcription-polymerase chain reaction; the fibronectin primers encompassed the alternatively spliced EIIIA exon. The levels of alpha 1 (IV) collagen and fibronectin mRNAs were measured relative to an internal standard (beta-actin mRNA). The proportion of EIIIA+ to EIIIA- fibronectin transcripts was similar in the retinas of control and galactose-fed rats, which, however, showed increased levels of both fibronectin and collagen IV mRNAs in the presence of unchanged beta-actin mRNA levels. An upward trend was detected by 5 weeks of galactose feeding; and after 9 weeks the fibronectin/actin ratio was 1.2 +/- 0.3 vs 0.8 +/- 0.2 in controls (p = 0.015) and the collagen IV/actin ratio was 1.3 +/- 0.3 vs 0.9 +/- 0.2 in controls (p = 0.04). Thus, hyperhexosaemia of a few weeks' duration is a perturbation sufficient to increase the synthesis of basement membrane components in the retina. The search for additional early biosynthetic changes should assist in reconstructing the pathogenesis of hexose-induced retinal microangiopathy.
Roy
S
S
Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA.
Lorenzi
M
M
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000821:Animal Feed; D000818:Animals; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers; D003720:Densitometry; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004195:Disease Models, Animal; D005353:Fibronectins / Q000096:biosynthesis* / Q000235:genetics; D005690:Galactose / Q000008:administration & dosage; D005693:Galactosemias / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D012160:Retina / Q000737:chemistry
D000199:Actins; D017931:DNA Primers; D005353:Fibronectins; D012333:RNA, Messenger; D003094:Collagen; D005690:Galactose