Temporal Relationship Between Successful Pancreas Transplantation and Control of Ocular Complications in Alloxan-Induced Diabetic Rats

doi:10.1016/j.transproceed.2008.01.049

Transplantation Proceedings

Volume 40, Issue 2, March 2008, Pages 518-523

https://doi.org/10.1016/j.transproceed.2008.01.049 Get rights and content

Abstract

Purpose

The impact of pancreas transplantation (PT) on the progression of eye disease is still controversial. This study evaluated the course of retinopathy in transplanted rats in two different diabetic stages.

Methods

Sixty inbred male Lewis rats were assigned to four experimental groups: NC—15 nondiabetic control rats; DC—15 untreated diabetic control rats; PT₁—15 diabetic rats that received syngeneic pancreas transplants 2 weeks after alloxan diabetes induction; PT₂—15 diabetic rats that received pancreas transplants 12 weeks after diabetes onset. Clinical and laboratory parameters and lens opacity were examined in all rats prior to treatment and at 1-, 6-, and 12-months follow-up. Nucleated eyes from five rats in each group processed for ultrastructural study of the retinal at 6 and 12 months after PT or at follow-up.

Results

Cataracts were observed in 20%, 60%, and 100% of DC rats at 1-, 6-, and 12-months follow-up, respectively. Early PT (2 weeks) significantly reduced the prevalence of this complication but not late (12 weeks) PT. PT₁ rats also showed improved ultrastructure of the superficial and deep capillary plexuses of the retina, and of Müller cells, compared with DC and PT₂. In the last group, retinopathy continued to evolve despite successful PT.

Conclusion

Our results suggested that prevention of diabetic ocular lesions by PT was closely dependent on earlier performance of the procedure.

Section snippets

Animals and Groups

Sixty inbred male Lewis rats, approximately 3 months old, were randomly assigned to four experimental groups (n = 15): NC—nondiabetic control group; DC—untreated diabetic control group; PT₁—diabetic group receiving syngeneic pancreas transplants at 2 weeks after diabetes induction; and PT₂—diabetic group receiving syngeneic pancreas transplants at 12 weeks after diabetes onset. Normal inbred Lewis rats were used as donors for both transplanted groups.

Diabetes was induced by intravenous

Clinical Findings

Nondiabetic control rats (NC) showed clinical and laboratory parameters within normal ranges throughout the study. In contrast, untreated diabetic control rats (DC) revealed significantly increased water and food intakes, urine outputs, blood glucose, and glycated hemoglobin levels compared to NC rats. Also, plasma insulin was significantly decreased in DC rats. All metabolic parameters in successful pancreas-transplanted rats (PT₁ and PT₂), including hemoglobin A1c (Figure 1) were restored to

Discussion

The metabolic changes caused by diabetic status affect all organs and systems. The retina, one of the organism’s high-metabolism tissues, is also sensitive to the consequences of these alterations. Diabetes in rats induces morphological and ultrastructural changes in crystalline and retinal vessels similar to those observed in humans and other mammals.⁸

In our study M, E, and P retinal cells were equally affected in all untreated diabetic control rats. The diabetic lesions were characterized by

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Unfortunately, there are no studies in the literature where the effects of PT on pulmonary lesions have been studied. However, PT has been shown to be capable of controlling chronic diabetic lesions in the kidneys,21,22 eyes,23 and nerves24 of diabetic humans and other animals, although there is probably a “point of no return” for diabetic complications despite treatment, as seen by us in the retina.13 Our results confirm that PT currently seems to be the only known therapy to reliably reestablish endogenous insulin secretion responsive to normal feedback controls, although this is achieved in clinical practice at the expense of a not always risk-free immunosuppression.
The aim of this study was to evaluate whether pancreas transplantation (PT) is a suitable method for controlling histopathologic changes in lungs of alloxan-induced diabetic rats.
Sixty inbred male Lewis rats were randomly assigned to 3 experimental groups: NC, 20 nondiabetic control rats; DC, 20 untreated diabetic control rats; and PT, 20 diabetic rats that received syngeneic PT from normal donor Lewis rats. Each group was further divided into 2 subgroups of 10 rats each, which were killed after 4 and 12 weeks of follow-up. Clinical and laboratory parameters, fresh and fixed lung weights, and fixed lung volumes were recorded for all rats. Total number of alveoli, alveolar perimeter, alveolar surface area, and alveolar epithelial (AE) and endothelial capillary (EC) basal laminae thickening were randomly measured in 5 rats from each subgroup by using an image analyzer. For light microscopy, 250 alveoli were analyzed in each subgroup. For electron microscopy, 50 electron micrographs were examined for each subgroup.
The DC rats showed elevated blood glucose and glycosylated hemoglobin levels, with insulin blood levels significantly lower than the NC rats (P < .001). Fresh and fixed lung weights and fixed volumes were significantly reduced in these rats, although their proportions to body weight were increased at 12 weeks (P < .01). The total number of alveoli in diabetic rats was higher than in control rats, whereas alveolar perimeter and surface area were significantly diminished (P < .01). AE and EC basal laminae were significantly thicker in DC than in NC (P < .01). Successful PT corrected all clinical and metabolic changes in diabetic rats, with sustained normoglycemia throughout the study. Morphologic and morphometric changes observed in diabetic lungs were completely prevented in PT rats from 4 weeks after transplant.
We conclude that PT can control morphologic and ultrastructural changes in pulmonary parenchyma, suggesting a promising perspective for preventing other chronic diabetic lesions.
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: Research supported by Fapesp.

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PancreasWhole pancreas transplantation: ExperimentalTemporal Relationship Between Successful Pancreas Transplantation and Control of Ocular Complications in Alloxan-Induced Diabetic Rats

Abstract

Purpose

Methods

Results

Conclusion

Section snippets

Animals and Groups

Clinical Findings

Discussion

Ophthalmology

Mol Cell Biol Res Commun

Exp Eye Res

Lancet

Ophthalmology

Intensive insulin regimens: evidence for benefit

Int J Obes Relat Metab Disord

Issues surrounding tight glycemic control in people with type 2 diabetes mellitus

Ann Pharmacother

Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus

N Engl J Med

The effect of whole organ pancreas transplantation and PIT on diabetic complications

Curr Diab Rep

Pancreaticoduodenal transplantation in the rat

Transplantation