Bioengineering Approaches for the 3D Blood-Retinal Barrier: Disease Modeling and Drug Development

The integrity and functionality of the blood-retina barrier (BRB) are essential for maintaining homeostasis of the retina. Disruption of the BRB is a key feature in different stages of retinal diseases including diabetic retinopathy, age-related macular degeneration (AMD), and inherited retinal diseases such as retinitis pigmentosa. In order to understand and recapitulate various retinal diseases, there has been significant interest in the progress of in vitro 3D-BRB models as they may address limitations associated with traditional 2D cultures and xenogeneic animal models. Therefore, it is crucial to explore 3D in vitro models for investigating mechanistic and therapeutic strategies in BRB-related diseases. In this review, we provide an overview of recent advances in BRB models, ranging from simple constructs to complex systems. In this review, commonly used techniques (extracellular matrix scaffolds, 3D bioprinting, and microfluidics), cell types utilized, and biomaterials employed are discussed. Additionally, we focus on new developments over the past three years, emphasizing applications of 3D-BRB models in disease evolution and drug screening. Overall, 3D modeling for the BRB holds promise for recapitulating the structural and functional characteristics of the in vivo BRB, which is a powerful armament for laboratory research and translational medicine for retinal diseases.