Blocking CXCR3 with AMG487 ameliorates the blood-retinal barrier disruption in diabetic mice through anti-oxidative

Area of Science:

• Ophthalmology
• Endocrinology
• Immunology

Background:

• Diabetic retinopathy (DR) involves oxidative stress and blood-retinal barrier (BRB) damage from hyperglycemia.
• CXC chemokine receptor 3 (CXCR3)-mediated inflammation is implicated in various disease models.

Purpose of the Study:

• To investigate if AMG487, a CXCR3 antagonist, can reduce BRB disruption and reactive oxygen species (ROS) in a diabetic retinopathy model.

Main Methods:

• Evaluated retinal endothelial and ganglion cell ultrastructure via transmission electron microscopy.
• Assessed pericyte marker PDGFR-β, tight junction occludin, albumin leakage, oxidative stress, CHOP, and p-p38 expression in vivo and in vitro.
• Utilized a streptozocin-induced diabetic retinopathy mouse model.

Main Results:

• AMG487 application potentially mitigated PDGFR-β and occludin loss in the DR mouse model.
• AMG487 decreased retinal albumin content by inhibiting oxidative and endoplasmic reticulum stress.
• p38 activation was identified as a factor involved in the observed effects.

Conclusions:

• CXCR3 inhibition with AMG487 may offer a protective effect against early diabetic retinopathy.
• Targeting CXCR3 could be a viable strategy for preventing diabetic retinopathy-induced retinal injury.