Methods of treating eye disorders with aplnr antagonists and VEGF inhibitors
An antagonist, eye disease technology, applied in chemical instruments and methods, antibody medical ingredients, medical preparations containing active ingredients, etc., can solve problems such as vascular permeability, neovascular vascular dysfunction, etc.
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[0174] The following examples are presented to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the methods and compositions of the present disclosure, and are not intended to limit the scope of what the inventors believe to be their disclosure. Efforts have been made to ensure accuracy with respect to numbers used (eg, amounts, temperature, etc.), but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is average molecular weight, temperature is in degrees Celsius, and pressure is at or near atmospheric.
example 1
[0176] To assess the in vivo properties of selected anti-APLNR antibodies of the disclosure, their ability to block APLNR-mediated angiogenesis in ocular vasculature was measured.
[0177] The retinal vascular development (RVD) model was used to assess the effect of an antagonistic anti-APLNR antibody on the outgrowth of blood vessels in the normally developing retina of mouse pups of mixed background strains (75% C57BL6 and 25% Sv129) and was used to express human APLNR Homozygous replacement of mouse APLNR (humanized APLNR mouse).
[0178] Humanized (Hu) ApelinR mice were injected systemically (IP) with 25 mg / kg and 50 mg / kg anti-Apelin receptor antibody (αAR; H2aM9232N) on postnatal (P) day 2. Reagents were blinded and labeled Solution A and Solution B to prevent experimenter bias. At postnatal day 5, tissue samples were collected and then fixed in PBS containing 4% paraformaldehyde. Fixed tissue samples (retinal endothelial cells) were washed with PBS and subsequently tr...
example 2
[0182] Similar to Example 1, subsequent experiments were performed in the RVD model at the highest dose and analyzed by single-blind grader. Briefly, pups were injected IP with 50 mg / kg Fc (control) or aAR. Figure 2A and 2B are representative photomicrographs and calculated vessel area maps of systemically treated mouse retinas at P2 to P5. Residual vessel area was significantly smaller in αApelinR retinas compared to untreated retinas (35% at 50 mg / kg, p<0.005). Retinal endothelial cells were stained with GS lectin I. Images were taken at 2Ox (for quantification) and 4Ox. Statistical analysis was performed using Student's T-test. Selective inhibition of ApelinR by systemic injection delays normal vascular outgrowth in the developing retina of P5 pups. Targeting ApelinR further delayed retinal vessel outgrowth by increasing the dose to a 50mg / kg dose.
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