A New Therapy for Early Diabetic Retinopathy (EDR) With Intravitreal Injection of LCVS1001

Abstract

Purpose:: To explore protective effects of LCVS1001, a glycoprotein, on EDR in Streptozotocin (STZ) induced diabetic rats.

Methods:: Diabetes was induced in SD rats by STZ (i.p.). A single intravitreal injection of LCVS1001 (8mU ~ 160mU/eye) was given either at 1 (group 1) or 4 weeks (group 2) after diabetes onset. The eyes were examined at 2 weeks after injection in Group 1 or 2 and 5 weeks after injection in Group 2. The blood-retinal barrier (BRB) was monitored by Evans blue. Apoptosis was detected by TUNEL. The retinal thickness and cell counts in different layers were evaluated with light microscopy. EM was used to scrutinize vascular and neuronal injury.

Results:: In LCVS1001-treated STZ-rats (Groups 1&2), BRB permeability was maintained at the non-diabetic control level. TUNEL-positive cells significantly increased in outer nuclear layer (ONL) at 3 weeks after diabetes onset. After 6 weeks, TUNEL-positive cells were also detected in inner nuclear layer (INL). In Group 1, no evident TUNEL-positive cell was detected in both ONL and INL at 2 weeks after LCVS1001 injection. This protective effect was similar in Group 2. The retinal thickness of different layers was reduced with diabetes-duration dependent fashion. The cell counts of both ONL and INL were reduced accordingly in the diabetic rats. LCVS1001 (16mU ~ 32mU/eye) prevented the cell loss and maintained a normal thickness in Groups 1 & 2. EM demonstrated that the death of photoreceptors was much ameliorated in the treated groups.

Conclusions:: Apoptosis of retinal neurons is a critical constituent in EDR. Intravitreal injection of LCVS1001 protects BRB function and retinal neurons from death. Therefore, LCVS1001 appears to be a novel approach for treatment of EDR.

Keywords: apoptosis/cell death • diabetic retinopathy • injection