Abstract
Purpose :
Prorenin has been viewed as an ideal target molecule in preventing diabetes mellitus (DM)-related microangiopathies. However, none of drugs can specifically inhibit prorenin activation. Here we employed peptide vaccine technique and tested the effect of prorenin peptide vaccine (VP) in murine models of type 2 diabetes mellitus (DM)
Methods :
VP was prepared by conjugating selected antigen from prorenin prosegment to keyhole limpet hemocyanin (KLH). C57BL/6J underwent 2× injection of KLH only (as control vaccine), peptide E1-conjugated with KLH (E1-KLH), E2-KLH or E3-KLH to optimize Vp. Then, mice underwent 3× vaccination. For three groups; db/db+KLH, db/db+VP and db/m+KLH, electroretinogram (ERG) and histological analyses were performed to assess the effect of VP.
Results :
E2-KLH was determined as VP in subsequent experiments between three candidate vaccines. Specific immunoreactivity of anti-sera from VP-immunized C57BL/6 mice against prorenin and BSA-conjugated E2, but not renin. Subcutaneous injection of 20 µg VP prevented the prolongation of implicit time of b-wave in db/db mice (p <0.05). VP significantly reduced the number of iba-1 positive activated microglia in the retina of db/db mice compared to db/db+KLH (p < 0.05). Furthermore, histological analysis demonstrated that VP mitigated glomerular and tubular expansion in the kidney and fatty liver. VP did not affect body weight, glucose levels and blood pressure.
Conclusions :
Vaccination against prorenin is effective and safe in protecting the retina from insults due to type 2 DM.
This is a 2021 ARVO Annual Meeting abstract.