Intravitreal CendR peptides target laser-induced choroidal neovascularization sites in mice

• DOI: 10.1016/j.jconrel.2023.07.025
• Publication Date: 2023-07-25T15:14:00Z
• Authors: Jooseppi Puranen; Sonja Korhonen; Maarja Haugas; Prakash Lingasamy; Tambet Teesalu; Astrid Subrizi; Arto Urtti; Marika Ruponen; Mika Reinisalo
• Keywords: C -end rule; Vascular Endothelial Growth Factor A; Targeting; Choroid; Lasers; Integrin; Pharmacy; Choroidal Neovascularization; Retina; 3. Good health; Mice, Inbred C57BL; Mice; Disease Models, Animal; Peptide; Tenascin C; Intravitreal Injections; Neuropilin; Animals; Peptides; Neovascularization

Choroidal neovascularization (CNV) is a common ocular pathology that may be associated in a variety of eye diseases. Although intravitreal injection treatment of anti-vascular endothelial growth factor (anti-VEGF) drugs shows significant clinical benefits in CNV treatment, the limitations of the current therapy need to be addressed. The aim of our study was to investigate the potential utility of three C-end Rule (CendR) peptides (RPARPAR, PL3, iRGD) for CNV targeting and to evaluate the efficacy of peptides for treating experimental CNV in mice. We observed that the CendR peptides localize to the CNV lesion sites after intravitreal injection and were mainly found in the outer nuclear cell layer (ONL) of the mouse retina. Interestingly, experimental therapy with tenascin-C (TNC-C) and neuropilin-1 (NRP-1)-targeting PL3 peptide, reduced angiogenesis and decreased vascular leakage. The results suggest that PL3 and potentially other CendR peptides could serve as affinity targeting ligands and therapeutics for ocular diseases that involve pathological CNV.