Scientists emulate the human blood-retinal barrier on a microfluidic chip

January 24, 2018, Autonomous University of Barcelona
Cells on the chip. Credit: José Yeste. (CSIC-IMB_CNM)

For some years, scientists have been seeking ways to reduce animal testing and accelerate clinical trials. In vitro assays with living cells are an alternative, but have limitations, as the interconnection and interaction between cells cannot be easily reproduced.

To overcome that, scientists are developing systems that mimic tissues and organ functions in conditions very close to reality. These so-called "organ-on-chip" devices include microenvironments and microarchitectures that emulate living organs and tissues.

Now, a team of scientists in Barcelona has developed a microfluidic device that mimics the human blood-retinal barrier. The scientists are from the Spanisch Council for Scientific Research (CSIC), the CIBER-BBN, and from the Institute of Health Carlos III, and the Universitat Autònoma de Barcelona (UAB). Their study, published in Lab-on-a chip, is a proof of concept that demonstrates the feasibility of the design.

Emulating the structure of the blood-retinal barrier

José Yeste, the main author of the study, explains that the device is composed of several parallel compartments arranged to emulate the retinal layer structure. In every compartment, a type of cell has been cultured—endothelial cells, which constitute capillary vessels which carry oxygen and nutrients; , which form the neuroretina; and retinal pigmented , which form the outer layer of the blood-retinal barrier.

The compartments are interconnected by a grid of microgrooves below, with which cells can exchange signal molecules and therefore communicate. As a result, substances produced by some cells can reach the other cells, generating cellular communication and interaction as in a living organ. Also, the device exposes endothelial cells to particular mechanical conditions that are similar the ones induced by the blood stream.

The new chip developed by Barcelona researchers. Credit: Jose Yuste (CSIC-IMB-CNM)

Rosa Villa, a leader of the Biomedical Applications Group, explains, "In the living organism, that cover the inner walls of blood vessels are exposed to the mechanical stimulus of the blood stream. In the cell cultures where this condition is not reproduced, the cells are 'sleepy,' and do not react as they would do in real conditions."

Rafael Simó, who leads the Diabetes and Metabolism group of the Vall d"Hebron Research Institute (VHIR), says, "The most relevant characteristic of this technology is that mimics what happens 'in vivo' in the retina and therefore can be an essential tool to boost the in vitro experimentation. On the device, the cells grow in contact with a fluid, as happens in the . Also, the cells have a close interaction via chemical mediators, which makes it possible to see what happens in a type of cell when another type of cell nearby is harmed. Also, it is possible to measure electrical resistance for assessing the functionality of the retinal neurons."

The scientists tested the correct formation of the blood-retinal barrier assessing its permeability, its electrical resistance and the expression of some proteins of the tight junctions between cells, which are expressed when cells have established a barrier function.

The tests have been designed to check whether the barrier was properly formed, but keeping the natural permeability to allow the pass of nutrients and oxygen, and to find out if the were in contact and interacting. This device, the scientists say, can be used to study the effects of molecules or harmful conditions on the human retina. The team also wants to use the device to study the diabetic retinopathy, a disease whose causes and progression are not well understood yet.

Previously, the team lead by Rosa Villa at the Microelectronics Institute of Barcelona (IMB-CNM) of the CSIC created a that emulates the blood-brain barrier. Also, they developed a liver-on-a chip microfluidic chamber that mimics the hepatic microcirculation.

Explore further: Reproducing a retinal disease on a chip

More information: Jose Yeste et al, A compartmentalized microfluidic chip with crisscross microgrooves and electrophysiological electrodes for modeling the blood–retinal barrier, Lab on a Chip (2017). DOI: 10.1039/C7LC00795G

Related Stories

Reproducing a retinal disease on a chip

June 15, 2017
Approximately 80% of all sensory input is received via the eyes, so suffering from chronic retinal diseases that lead to blindness causes a significant decrease in the quality of life (QOL). And because retinal diseases are ...

An organ-on-a-chip device that models heart disease

January 2, 2018
When studying diseases or testing potential drug therapies, researchers usually turn to cultured cells on Petri dishes or experiments with lab animals, but recently, researchers have been developing a different approach: ...

Scientists discover key regulator of blood vessel formation

August 29, 2017
New blood vessels branch out of preexisting ones is via a process called angiogenesis. Although this is essential for survival, development and wound healing, on the flip side, it also feeds and progresses malignant tumors, ...

Loss of pericytes deteriorates retinal environment

May 16, 2017
Inside the eye, at the interface between blood vessels and the retina, lies a boundary that prevents harmful substances present in the blood from entering the retina. Researchers at the Center for Vascular Research, within ...

Diabetic blindness caused and reversed "trapped" immune cells in rodent retinas

January 3, 2018
Johns Hopkins researchers have discovered a cell signaling pathway in mice that triggers vision loss in patients with diabetic retinopathy and retinal vein occlusion – diseases characterized by the closure of blood vessels ...

Blood brain barrier on a chip could stand in for children in pediatric brain research

December 5, 2014
In the human brain, the BBB is not the Better Business Bureau but the blood brain barrier and the BBB is serious business in human physiology. The human BBB separates circulating blood from the central nervous system, thus ...

Recommended for you

Foods combining fats and carbohydrates more rewarding than foods with just fats or carbs

June 14, 2018
Researchers show that the reward center of the brain values foods high in both fat and carbohydrates—i.e., many processed foods—more than foods containing only fat or only carbs. A study of 206 adults, to appear June ...

3-D imaging and computer modeling capture breast duct development

June 14, 2018
Working with hundreds of time-lapse videos of mouse tissue, a team of biologists joined up with civil engineers to create what is believed to be the first 3-D computer model to show precisely how the tiny tubes that funnel ...

Beating cancer at its own game with a Trojan horse telomerase

June 13, 2018
Telomerase is a reverse transcriptase that uses an RNA template to synthesize telomeres. These repeat sequences bind special proteins that fold the ends of chromosomes back onto themselves to create a stable cap. When this ...

Turning the tables on the cholera pathogen

June 13, 2018
Recent cholera outbreaks in regions that are ravaged by war, struck by natural disasters, or simply lack basic sanitation, such as Yemen or Haiti, are making the development of new and more effective interventions a near-term ...

Troves from a search for new biomarkers: blood-borne RNA

June 12, 2018
It's the critical first step in treating everything from strokes to cancer: a timely and accurate diagnosis. Today, doctors often rely on biomarkers, such as cardiac troponin, the protein that appears in the blood after a ...

High-tech treatment of open leg wounds no better than using regular dressings: study

June 12, 2018
A new study of open leg fractures suggests there is no difference to patient recovery whether high-tech negative pressure wound therapy devices are used, compared to standard dressings.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.