Some effects of aldose reductase inhibition upon the eyes of long-term streptozotocin-diabetic rats

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Abstract
The effects of a potent aldose reductase inhibitor, ICI 105552, (l-(3,4-dichloro-benzyl)-3-methyl-1,2-dihydro-2-oxoquinol-4-ylacetic acid), upon the development of cataract in streptozotocin-diabetic rats were followed for 11 months. Daily intubation with ICI 105552 at 50 mg/kg body weight delayed the onset and rate of development of cataract considerably. The time taken for 50% of eyes to show cataract more severe than a few small punctate opacities exceeded 320 days, at least 170 days longer than in placebo-dosed diabetics. Only 4 eyes of inhibitor-dosed rats developed complete cataract as assessed in vivo; dissection post mortem showed these lenses to be less degenerated than those of placebo-dosed diabetics. At day 149, progression of cataract beyond traces of opacity had occurred in all placebo-dosed diabetics. In certain diabetics dosed with ICI 105552 such progression did not occur even after 324 days of treatment. Intra-ocular haemorrhage developed in 8 of 14 eyes of placebo-dosed diabetics surviving 245 treatment days but was never evident in ICI 105552-dosed diabetics. ICI 105552 may therefore be suitable for long-term studies of the pathogenesis of certain complications secondary to diabetes.