ADM-RAMP2 system could be therapeutic target for retinal vein occlusion

A model of central retinal vein occlusion (CRVO) in mice that mimics the clinical features of CRVO in humans was used to study the pathologic effects of retinol occlusion and demonstrate the retinoprotective effects of the peptide adrenomedullin (ADM) and the protein RAMP2.

“CRVO is the second most common retinal vascular disease next to diabetic retinopathy. In recent years, intravitreal administration of anti-vascular endothelial growth factor (VEGF) agents has been used to treat CRVO by suppressing retinal vascular permeability. However, recurrence of macular swelling and decreasing drug effectiveness are limitations of this approach.

“Therefore, identification of other therapeutic agents that enhance vascular integrity is desirable. In this study, we proved that the ADM-RAMP2 system is one of the novel therapeutic targets for treatment of CRVO,” explained Dr Takayuki Shindo, of the Department of Cardiovascular Research at Shinshu University Graduate School of Medicine, Matsumoto, Japan.

The researchers generated a CRVO model by combining intraperitoneal injection of Rose Bengal – a photo-activator dye that enhances thrombus formation with laser photocoagulation. The team noticed that the most prominent changes were retinal hemorrhage and venous dilatation with tortuosity. They went on to measure retinal thickness, which revealed prominent oedema early after CRVO was induced, followed by gradual atrophy.

Retinal vein occlusion affects around 16.4 million people worldwide and often occurs as a complication of ageing, diabetes, hypertension or dyslipidemia. Features used to diagnose patients are inflammation, hemorrhage, capillary loss, and other vascular complications. 

The mentioned that there are several ways that ADM works in CRVO, and was initially identified as a vasodilating peptide that was expected to improve blood flow in CRVO. The results of the study showed how ADM suppressed inflammation and oxidative stress associated with CRVO. The team also found that ADM also suppresses vascular hyperpermeability, which is the cause of retinal edema, and increases vascular reperfusion.

“As the biological functions of ADM are likely different from VEGF antibodies, co-administration of ADM and VEGF antibodies may be a choice in some diseases. It may also be used as secondary therapy when patients become resistant to VEGF antibodies,” stated Dr Shindo.

Based on the results of the study the research team propose that the retinoprotectivity of the ADM-RAMP2 system make it a novel therapeutic target for the treatment of CRVO.

The study was published in the Ameircan Journal of Pathology.