Abstract

Aims We investigated the changes of retinal structure in normal glucose tolerance (NGT), impaired glucose tolerance (IGT), diabetes mellitus (DM), and diabetic kidney disease (DKD) stages in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods We assigned OLETF rats to four groups based on their OGTT results and 24 h urinary microalbumin (24 h UMA) levels: NGT, IGT, DM, and DKD groups. We observed the structural and the corresponding pathological changes and quantified the expression of HIF-1α, iNOS, NF-κB, VEGF, ICAM-1, and occludin in the retina. Results Significant damage to the retinal structure, especially in retinal ganglion cells (RGCs), was observed in the IGT stage. The expression of HIF-1α, iNOS, NF-κB, VEGF, and ICAM-1 was significantly upregulated, while that of occludin was downregulated. Conclusion Significant retinal neuropathy occurs in the IGT stage. Inflammation and hypoxia may damage the blood retina barrier (BRB), leading to diabetic retinopathy.

Highlights

  • With the increasing prevalence of diabetes, chronic complications, especially diabetic kidney disease (DKD) and retinopathy (DR), pose serious social problems threatening human health

  • The expression levels of Tumour necrosis factor-α (TNF-α) and IL-6 were increased in the impaired glucose tolerance (IGT) stage and continued to increase with the progression of the disease (P < 0:05)

  • The levels of 24 h UMA were similar in the normal glucose tolerance (NGT), IGT, and diabetes mellitus (DM) groups but were higher in the DKD group than in the other groups (Table 1)

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Summary

Introduction

With the increasing prevalence of diabetes, chronic complications, especially diabetic kidney disease (DKD) and retinopathy (DR), pose serious social problems threatening human health. The overall prevalence of DR, the primary retinal vascular complication of diabetes mellitus (DM), is 34.6% for any DR in DM. It is a leading cause of vision impairment and blindness in the working-age population [1,2,3]. Our previous studies focused on the structural and functional damage to the renal tubule in the impaired glucose tolerance (IGT) stage [13]. As DR may occur at an earlier stage of diabetes, we analyzed the structural alterations of the retina in different stages of diabetes and investigated the pathogenesis of DR in Otsuka Long-Evans Tokushima Fatty (OLETF) rats

Methods
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