Early biosynthetic changes in the diabetic-like retinopathy of galactose-fed rats

Diabetologia. 1996 Jun;39(6):735-8. doi: 10.1007/BF00418547.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / biosynthesis
  • Actins / genetics
  • Animal Feed
  • Animals
  • Collagen / biosynthesis*
  • Collagen / genetics
  • DNA Primers
  • Densitometry
  • Diabetic Retinopathy / metabolism*
  • Disease Models, Animal
  • Fibronectins / biosynthesis*
  • Fibronectins / genetics
  • Galactose / administration & dosage
  • Galactosemias / genetics
  • Galactosemias / metabolism*
  • Gene Expression
  • Male
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Reference Standards
  • Retina / chemistry

Substances

  • Actins
  • DNA Primers
  • Fibronectins
  • RNA, Messenger
  • Collagen
  • Galactose

Associated data

  • GENBANK/J00691
  • GENBANK/U10557
  • GENBANK/X15906