Abstract
The blood-retinal barrier (BRB) protects the retina by maintaining an adequate microenvironment for neuronal function. Alterations of the junctional complex of the BRB and consequent BRB breakdown in disease contribute to a loss of neuronal signaling and vision loss. As new therapeutics are being developed to prevent or restore barrier function, it is critical to implement physiologically relevant in vitro models that recapitulate the important features of barrier biology to improve disease modeling, target validation, and toxicity assessment. New directions in organ-on-a-chip technology are enabling more sophisticated 3-dimensional models with flow, multicellularity, and control over microenvironmental properties. By capturing additional biological complexity, organs-on-chip can help approach actual tissue organization and function and offer additional tools to model and study disease compared with traditional 2-dimensional cell culture. This review describes the current state of barrier biology and barrier function in ocular diseases, describes recent advances in organ-on-a-chip design for modeling the BRB, and discusses the potential of such models for ophthalmic drug discovery and development.
Highlights
The blood–retinal barrier (BRB) helps to maintain the proper retinal environment to allow vision and is dysfunctional in several blinding eye diseases.[1]
In ocular diseases such as diabetic retinopathy and agerelated macular degeneration (AMD), alterations of the junctional complex of the BRB and consequent BRB breakdown may contribute to a loss of neuronal signaling and neural apoptosis.[1,7]
Phosphorylation and internalization of VE-cadherin, a major constituent of the adherens junctions, contributes to vascular endothelial growth factor (VEGF)-induced permeability.[37]. These results show that VEGF signaling at the endothelial cells of the inner BRB (iBRB) induces alterations of the junctional complex, with the most prominent effects being vesicle-mediated internalization of the complex and increased vascular permeability
Summary
The blood–retinal barrier (BRB) helps to maintain the proper retinal environment to allow vision and is dysfunctional in several blinding eye diseases.[1]. The inner BRB (iBRB) is composed of specialized retinal vascular endothelial cells that have well-developed tight junctions (TJ) and limited transcellular vesicles that restrict nonspecific transport from the vascular circulation, and the outer BRB (oBRB) is made of the retinal pigmented epithelium that controls flux from choriocapillaries.[3] The BRB maintains the retina as a privileged site and controls the retinal environment to preserve neuronal function.[4,5,6] In ocular diseases such as diabetic retinopathy and agerelated macular degeneration (AMD), alterations of the junctional complex of the BRB and consequent BRB breakdown may contribute to a loss of neuronal signaling and neural apoptosis.[1,7] New treatments in ophthalmology are focusing on restoring the barrier function and/or limiting vascular leakage by targeting mediators of barrier dysfunction. We review the current state of barrier biology and barrier function in ocular diseases, describe current organson-chip to model the BRB, and highlight their potential for ophthalmic drug development
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
