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Evidence Supporting Autotaxin as a Potential New Drug Treatment Target in Patients With Advanced Diabetic Retinopathy
Harumasa Yokota1,2, Hiroki Hayashi3, Hironori Nakagami3
1Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.
Purpose:
The purpose of this study was to test the hypothesis that increased intraocular autotaxin (ATX) levels contribute to the progression of diabetic retinopathy (DR), we investigated ATX levels in the vitreous of patients with type 2 diabetes with proliferative diabetic retinopathy (PDR) and assessed the effect of an ATX peptide vaccine (VA) in a db/db mouse model of type 2 diabetes.
Methods:
Vitreous samples were collected from participants with PDR and from controls with non-diabetic ocular diseases. ATX, lipid mediator, and cytokine levels were measured by ELISA. VA or a control vaccine was administered to db/db mice at 7 and 9 weeks of age. Antibody titers were quantified at 15 weeks of age. Retinal function and blood flow responses to systemic hyperoxia and flicker stimulation were assessed every 2 weeks from age 10 to 14 weeks using electroretinography (ERG) and laser speckle flowgraphy.
Results:
Vitreous ATX levels were significantly higher in PDR than in epiretinal membrane or lens dislocation, and positively correlated with ICAM-1, TGF-β1, and adiponectin. VA improved blood glucose levels but not resting blood flow. However, VA restored blood flow responses to both hyperoxia and flicker stimulation and improved ERG implicit times compared with the control vaccine.
Conclusions:
Elevated ATX may contribute to the progression of advanced DR. Vaccination against ATX preserved neurovascular function in early diabetic retinopathy in mice. Further studies are needed to clarify its role in DR progression.
