Selective Targeting and Tissue Penetration to the Retina by a Systemically Administered Vascular Homing Peptide in Oxygen Induced Retinopathy (OIR)

Abstract

Pathological angiogenesis is the hallmark of ischemic retinal diseases among them retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR). Oxygen-induced retinopathy (OIR) is a pure hypoxia-driven angiogenesis model and a widely used model for ischemic retinopathies. We explored whether the vascular homing peptide CAR (CARSKNKDC) which recognizes angiogenic blood vessels can be used to target the retina in OIR. We were able to demonstrate that the systemically administered CAR vascular homing peptide homed selectively to the preretinal neovessels in OIR. As a cell and tissue-penetrating peptide, CAR also penetrated into the retina. Hyperoxia used to induce OIR in the retina also causes bronchopulmonary dysplasia in the lungs. We showed that the CAR peptide is not targeted to the lungs in normal mice but is targeted to the lungs after hyperoxia-/hypoxia-treatment of the animals. The site-specific delivery of the CAR peptide to the pathologic retinal vasculature and the penetration of the retinal tissue may offer new opportunities for treating retinopathies more selectively and with less side effects.

Proteomics Analysis of R-Ras Deficiency in Oxygen Induced Retinopathy

“…The eradication of the neovessels by VEGF inhibitors may even worsen the underlying ischemia in the retina and subsequently drive the formation of new blood vessels by alternative molecular mechanisms in the hypoxic retina [4,6]. Thus, a better understanding of the factors controlling the vascular permeability in retinopathy is required to develop nextgeneration drugs for more efficient and selective treatment of retinopathy [4,5,7]. These drugs should be selective in their function; they should stabilize the pathological leaky blood vessels to ones that carry oxygen to address the hypoxia in the retina without having pathological permeability [4,5,7].…”

Editorial on Special Issue “Precision Delivery of Drugs and Imaging Agents with Peptides”

“…The original contributions in this Special Issue address the development of internalizing peptides as facilitators of intracellular cargo uptake [ 1 , 2 , 3 ] as well as preclinical studies on homing peptide-guided molecular and nanoscale precision systemic drug delivery systems [ 4 , 5 , 6 , 7 , 8 ]. This thematic issue illustrates the current trends in the field of peptide-mediated affinity targeting.…”

“…This thematic issue illustrates the current trends in the field of peptide-mediated affinity targeting. The first is expansion of the range of target pathologies beyond cancer, illustrated by studies using CAR peptide as an affinity ligand to target retinal diseases [ 4 ] and cystic fibrosis lesions [ 5 ]. The second trend is increased reliance on the disease-associated isoforms of the extracellular matrix as targets for homing peptides [ 3 , 4 , 5 , 6 ].…”

“…The first is expansion of the range of target pathologies beyond cancer, illustrated by studies using CAR peptide as an affinity ligand to target retinal diseases [ 4 ] and cystic fibrosis lesions [ 5 ]. The second trend is increased reliance on the disease-associated isoforms of the extracellular matrix as targets for homing peptides [ 3 , 4 , 5 , 6 ]. Extracellular matrix has been emerging, in many respects, as an ideal target for affinity delivery due to its robust upregulation in reactive tissues, abundance, low shedding profile, and accessibility to circulating probes.…”

“…CAR recognizes the unique sulfation pattern of heparan sulfate proteoglycans on the target cells. The first study [ 4 ] coordinated by Dr. Tero Järvinen at Tampere University (Finland) addresses the relevance of the CAR peptide for targeting retinal diseases—a major cause for blindness in Western countries. The pharmacological treatment of these devastating diseases is hindered by poor bioavailability of drugs to the retina.…”