Diabetic retinopathy is one of the leading causes of
blindness in developed countries, and a majority of patients with type I and type II diabetes will develop some degree of vision loss despite
blood glucose control regimens. The effects of different
insulin therapy regimens on early metabolic, inflammatory and neuronal
retinal disease processes such as
retinal neuroinflammation and synapse loss have not been extensively investigated. This study compared 3 months non-diabetic and
streptozotocin (STZ)-induced diabetic Sprague Dawley rats. Diabetic rats received either no
insulin treatment, systemic
insulin treatment beginning after 1 week uncontrolled diabetes (early intervention, 11 weeks on
insulin), or after 1.5 months uncontrolled diabetes (late intervention, 6 weeks on
insulin). Changes in both whole animal metabolic and
retinal inflammatory markers were prevented by early initiation of
insulin treatment. These metabolic and inflammatory changes were also normalized by the later
insulin intervention.
Insulin treatment begun 1 week after diabetes induction ameliorated loss of
retinal synapse markers. Synapse markers and presumably synapse numbers were equivalent in uncontrolled diabetes and when
insulin treatment began at 1.5 months of diabetes. These findings are in agreement with previous demonstrations that
retinal synapses are lost within 1 month of uncontrolled diabetes and suggest that synapses are not regained with
glycemic control and restoration of
insulin signaling. However, increased expression of metabolic and inflammatory markers associated with diabetes was reversed in both groups of
insulin treatment. This study also emphasizes the need for
insulin treatment groups in
diabetic retinopathy studies to provide a more faithful modeling of the human condition.