Provided herein are Notch1 fusion proteins. These fusion proteins comprise consecutive amino acids the sequence of which, commencing at the N-terminus of the fusion protein, is identical to the sequence of the amino acids in an extracellular domain of a human Notchl receptor protein and an Fc portion of an antibody. The amino acid sequence of the extracellular domain (ECD) of the human Notchl receptor protein commences with the amino acid present at the N-terminus of EGF-like repeat (10) and extends at least through the C-terminal amino acid of EGF-like repeat (23). The N-terminal portion of the ECD of the human Notchl receptor protein may extend up to the C-terminal amino acid of EGF-like repeat (24) or may extend up to the C-terminal amino acid of EGF-like repeat (36). Compositions of these fusion proteins are also provided. Also provided are methods of treating age-related macular degeneration (AMD), diabetic retinopathy and cancer using the fusion proteins described herein.