**2. Next-generation DR models and conclusion**

The ideal animal model for DR would mimic the complete pathophysiological process of DR in humans, with initial development of NPDR features and gradual progression to PDR with or without macular edema in the presence of prolonged hyperglycemia. However, the majority of existing animal models only display early or advanced lesions of DR. DR has a complex etiology, with various genetic and environmental factors implicated in its disease susceptibility and progression. Animal models are particularly important for the screening of novel therapeutic interventions. The clinical application of gene therapy for DR has been garnering increasing interest, and this may call for animal models that better reflect the intricacies of DR pathogenesis. Mice and rats are highly genetically tractable, but current transgenic models are based on isolated crosses [92]. Increasing development and use of resources such as The Collaborative Cross [92] may be required to enhance future identification and development of mouse strains with complex traits and epigenetics that are more reflective of the clinical scenario. Only by identifying and manipulating genes that mediate clinically relevant phenotypes can we realize and exploit the full genetic tractability of the mouse to better model DR.
