An antisense oligonucleotide targeting the growth hormone receptor inhibits neovascularization in a mouse model of retinopathy

Abstract

Purpose: We have demonstrated that a 2′-O-methoxyethyl modified antisense oligonucleotide against the mouse growth hormone (GH) receptor (GHr), reduces GH binding and serum insulin-like growth factor-1 in normal mice. We tested whether this systemically delivered antisense oligonucleotide could inhibit neovascularization in mice with oxygen induced retinopathy (OIR). Methods: OIR was induced in C57BL/6 mice by housing them in 75% oxygen across postnatal days (P)7 to 12 followed by five days in room air. Shams were in room air from P0-17. GHr antisense oligonucleotide, ATL 227446, was administered by early (P7, 8, 9, 11, 13, 15, and 17) or late (P12-16) intervention at doses of 5, 10, 20, and..