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3-D ROC Awards & Recognition

Phase II Awardees

Image of Dr. Vergara

Vergara Team

NEI  awarded a team led by Maria Natalia Vergara, Ph.D., Sue Anschutz-Rodgers Eye Center, University of Colorado $60,000 for developing an organoid derived from stem cells engineered to fluoresce which allows the organoid to demonstrate the cellular composition more clearly and efficiently. This advancement allows for improved organoid differentiation that can be used to screen and validate drugs more readily.

Winning Team
  • Maria Natalia Vergara, Ph.D., University of Colorado
  • Maria Valeria Canto-Soler, Ph.D., University of Colorado Anschutz Medical Campus
  • Michael L. Robinson, Ph.D., Miami University 
  • Katia Del Rio-Tsonis, Ph.D., Miami University 
  • Samarendra Mohanty, Ph.D., Nanoscope Technologies, LLC
Vergara Team  Abstract 

The advent in the last decade of human stem cell-derived retinal organoid models opened unprecedented opportunities to improve the drug development pipeline by increasing efficiency and decreasing costs. These models enabled the possibility to test drug candidates in three-dimensional human retinal tissues that resemble the native scenario. However, to realize this promise we need robust protocols for retinal organoid differentiation that can increase assay reproducibility and decrease variability. Moreover, drug screening platforms necessitate fast, sensitive, and robust technologies that can provide quantitative information in longitudinal studies on live cells, something that has proven challenging when working with 3D tissues. Here we have addressed these challenges through the novel combination of robust technologies for organoid development and non-invasive, real time quantitative assessment. We have developed physiologically competent induced pluripotent stem cell (hiPSC)-derived retinal organoids that recapitulate to a large extent the histoarchitecture and cellular composition of the native human neural retina including the presence of all major retinal cell types, and that demonstrate for the first time the presence of all bipolar cell subtypes. The improved protocol produces light responsive organoids while increasing yield in organoid production and accelerating photoreceptor differentiation. Moreover, we have applied this protocol to a first-of-its-kind triple fluorescent reporter hiPSC line and combined it with our robust 3D Automated Reporter Quantification system. This unique combination results in a drug screening/validation platform that allows for non-invasive quantitative, longitudinal phenotypic assessment of retinal progenitors, ganglion cells, bipolar cells, and photoreceptors in live organoids. This novel paradigm will have a significant impact in the field of retinal research, overcoming the current obstacles for drug validation in 3D retina models and improving the efficiency of the drug development pipeline, thus accelerating therapeutic discoveries. Furthermore, we also present data demonstrating the power of our platform to increase our understanding of retina biology.

View the Vergara Team video abstract

Image of Dr. Liu

Liu Team

NEI awards a team led by Wei Liu, Ph.D., Albert Einstein College of Medicine $40,000 for developing two different types of organoids that advance our ability to replicate the native retina, one which is enriched for cone photoreceptors, a composition that is particular to the human retina, and the other organoid demonstrating RGC axon pathfinding abilities. These organoids have also been used to establish the feasibility of studying retinal diseases that lead to blindness such as Leber Congenital Amaurosis.

Winning Team
  • Wei Liu, Ph.D. , Albert Einstein College of Medicine 
  • Rupendra Shrestha, Ph.D., Albert Einstein College of Medicine 
  • Albert Lowe, Ph.D. Student, Albert Einstein College of Medicine
  • Rui Chen, Ph.D., Baylor College of Medicine
  • Sangbae Kim, Ph.D., Baylor College of Medicine
  • Z. Jimmy Zhou, Ph.D., Yale School of Medicine
  • Seunghoon Lee, Ph.D., Yale School of Medicine
  • Margaret M. DeAngelis, Ph.D., University of Utah
  • Ales Cvekl, Ph.D., Albert Einstein College of Medicine
Liu Team Abstract 

Retinal structures generated from stem cells are often immature, variable, and do not reflect the complexity of the human retina, such as cone enrichment in the macula and axon pathfinding of retinal ganglion cells (RGCs), furthermore the differentiation protocols used often limit their applications because of skills required and low efficiency. Here, we present a scalable system composed of cone-rich multilayered functional organoids, which model cone enrichment and RGC axon pathfinding in the human retina. Organoids with such complex features have not been reported by others and therefore are innovative. Transcriptome profiling and marker analysis indicate that retinal cell differentiation in our retinal organoids closely recapitulates how the retina develops in humans in temporal gene expression and alternative mRNA splicing. Cone enrichment in our retinal organoids is demonstrated by both quantitative immunostaining and single-cell RNA sequencing. Photoreceptors in our retinal organoids are substantially mature, as evidenced by the ultrastructure of outer segments, the expression of phototransduction genes, and electrophysiological functions. Our protocol is advantageous, as it does not require manual dissection, is highly efficient, and therefore is scalable. We have established the feasibilities of studying retinal disease genes that cause Leber Congenital Amaurosis and juvenile glaucoma using our system.

View the Liu Team video abstract 

October 2018 Check-In Winner

NEI awarded $25,000 to a team led by Wei Liu, Ph.D., Albert Einstein College of Medicine, for demonstrating progress toward the development of a living model of the human retina, the light-sensitive tissue at the back of the eye. 

Winning Team
  • Wei Liu, Ph.D., Albert Einstein College of Medicine
  • Albert Lowe, Albert Einstein College of Medicine
  • Rui Chen, Ph.D., Baylor College of Medicine
  • Sangbae Kim, Ph.D., Baylor College of Medicine
  • Z. Jimmy Zhou, Ph.D., Yale School of Medicine
  • Seunghoon Lee, Ph.D., Yale School of Medicine
  • Margaret M. DeAngelis, Ph.D., University of Utah
  • Ales Cvekl, Ph.D., Albert Einstein College of Medicine

Liu’s submission demonstrated the generation of mini retinas similar in composition to the human macula, a part of the retina used for central, high-resolution vision. Specifically, the mini retinas include cone photoreceptors, the type of light-sensing retinal cell needed for color vision.

Phase I Awardees

NEI awarded $90,000 in prize money to a team led by Erin Lavik, Sc.D., at the University of Maryland, Baltimore County, for its concept to create a living model of the human retina. Lavik’s team participated in the 3-D Retina Organoid Challenge (3-D ROC) “ideation” phase, which asked participants for ideas to generate human retinas from stem cells. Concepts were evaluated based on their innovativeness and feasibility. A review panel assessed how each proposal addressed scientific challenges such as how to assemble distinct and anatomically correct layers of retinal tissue, assess retinal cell function, and use the prototypes to understand diseases or test therapies. 

Winning Team
  • Erin Lavik, ScD, University of Maryland, Baltimore County
  • Steven Bernstein, MD, PhD, University of Maryland Medical School
  • Adam Day, University of Maryland, Baltimore County
  • Bryan Ibarra, University of Miami

The team’s idea is to build a retina by screen printing adult neural progenitor-derived retinal neurons in layers that mimic the structure of the human retina. The system is scalable and efficient which should enable the high reproducibility and increased throughput necessary for drug testing. 

Five teams were also recognized with honorable mention

Carrier Team

  • Rebecca Carrier, PhD, Northeastern University
  • Michael Young, PhD, Schepens Eye Research Institute
  • Joyce Y Wong, PhD, Boston University
  • Joydip Kundu, PhD, Northeastern University
  • Petr Baranov, MD, PhD, Schepens Eye Research Institute
  • Mike Ferguson, Boston University

Their organoid-microvessel co-culture system proposes to add vasculature embedded in a biomimetic hydrogel to organoids to increase oxygen and nutrient flow and mimic chemical and physical cues present in developing eye tissue. The system also includes retinal pigmented epithelium and can be used to model and study age-related macular degeneration (AMD). 

Gamm Team

  • David Gamm, MD, PhD, University of Wisconsin
  • William Murphy, PhD, University of Wisconsin
  • Nader Sheibani, PhD, University of Wisconsin
  • Chris Sorenson, PhD University of Wisconsin
  • Bikash Pattnaik, PhD, University of Wisconsin 
  • Melissa Skala, PhD University of Wisconsin

In the eye, the outer neural retina is fed via diffusion while the inner neural retina requires a separate microvasculature that is absent in organoids. This results in disparity in outer vs. inner neural retina survival and function in vitro. The team proposes to incorporate a perfusable inner retinal microvasculature using microfluidic technology and to model retinal microvascular diseases such as diabetic retinopathy.

Liu Team

  • Wei Liu, PhD, Albert Einstein College of Medicine
  • Rui Chen, PhD, Baylor College of Medicine
  • Z. Jimmy Zhou, PhD, Yale School of Medicine
  • Albert Lowe, Albert Einstein College of Medicine

The protocol efficiently generates retina organoids by altering key time-consuming variable steps. They propose to engineer additional retinal tissues on scaffolds and use the system to study Leber Congenital Amaurosis. 

Pelaez Team

  • Daniel Pelaez, PhD, University of Miami
  • J. William Harbour, MD, University of Miami
  • Zenith Acosta, University of Miami

The team’s novel tissue bioreactor system compartmentalizes and creates gradients of stimuli such that the maturation of inner and outer retinal cells are induced separately. The system recapitulates the normal physiology in which the retina is exposed to a steep gradient of oxygen tensions across the highly oxygenated outer retina, and the hypoxic inner retina and can be used to model Retinoblastoma. 

Schenke-Layland Team

  • Katja Schenke-Layland, PhD, Fraunhofer Institute for Interfacial Engineering and Biotechnology
  • Stefan Liebau, PhD, Eberhard Karls University Tübingen
  • Peter Loskill, PhD, Fraunhofer Institute for Interfacial Engineering and Biotechnology

The culture system proposed allows for 3-D co-culture of retinal organoids, retinal pigment epithelium (RPE) and further cell types in a defined and reproducible microenvironment, featuring a physiological vasculature-like perfusion for multiple weeks. Their 3-D Retina-on-a-chip system features 48 individual units in an integrated chip with standard well plate-dimensions that will be amenable for high content drug screening.

Last updated: January 31, 2021