Related Experiment Video
Updated: May 7, 2026
Trypsin Digest Protocol to Analyze the Retinal Vasculature of a Mouse Model
Published on: June 13, 2013
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.
Insights
Elevated autotaxin (ATX) in the eye may worsen diabetic retinopathy (DR). An ATX vaccine improved retinal function in a mouse model, suggesting a potential therapeutic target for DR.
Area of Science:
- Ophthalmology
- Endocrinology
- Immunology
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss.
- Autotaxin (ATX) is implicated in various ocular diseases.
- The role of intraocular ATX in DR progression is not fully understood.
Purpose of the Study:
- To investigate the hypothesis that increased intraocular autotaxin (ATX) levels contribute to diabetic retinopathy (DR) progression.
- To assess ATX levels in the vitreous of patients with proliferative diabetic retinopathy (PDR).
- To evaluate the therapeutic effect of an ATX peptide vaccine (VA) in a mouse model of type 2 diabetes.
Main Methods:
- Vitreous samples from PDR patients and controls were analyzed for ATX, lipid mediators, and cytokines.
- An ATX peptide vaccine (VA) or control vaccine was administered to db/db mice.
- Retinal function and blood flow were assessed using electroretinography (ERG) and laser speckle flowgraphy.
Main Results:
- Vitreous ATX levels were significantly higher in PDR patients and correlated with inflammatory markers.
- The ATX vaccine improved blood glucose control and restored retinal vascular responses to hyperoxia and flicker stimulation in mice.
- Vaccination improved electroretinography implicit times, indicating preserved neuroretinal function.
Conclusions:
- Elevated intraocular ATX may promote advanced DR progression.
- Vaccination against ATX demonstrated potential in preserving neurovascular function in early diabetic retinopathy.
- Further research is warranted to elucidate the role of ATX in DR and its therapeutic potential.
