Our previous study showed similar results that K5 downregulated VEGF much significantly in hypoxia than in normoxia in the oxygen-induced retinopathy model.29 The common features of diabetic retinopathy and tumour microenvironment are hypoxia, therefore we speculate that the effects of K5 on VHL, HIF-1α, and VEGF are more significant and suitable for the treatment of the diseases with hypoxia microenvironment (Supplementary Figure S5). This evidence concerns the gene HIF1A and diabetic retinopathy.