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.