Announcement of 3-D Retina Organoid Challenge (3-D ROC)

Notice Number: NOT-EY-18-006

Key Dates
Release Date: February 21, 2018

Related Announcements
NOT-EY-20-003

Issued by
National Eye Institute (NEI)

Purpose

The 3-D Retina Organoid' Challenge: Reduction to Practice (https://nei.nih.gov/3droc; the Challenge'), is an implementation prize competition in which the National Eye Institute (NEI; http://www.nei.nih.gov/), part of the National Institutes of Health (http://www.nih.gov), is asking for 3-D human retina culture systems with maximal relevance to human physiology and disease. Current retina culture models require over six months to develop and still do not capture the complexities of the human retina. The goal of the Challenge is to use innovative approaches to develop new in vitro 3-D human retina models that recapitulate the organization and function of the human retina and can be used to examine biology and disease processes. This challenge is a follow-on to the recent NEI 3-D Retina Organoid Ideation Challenge, and aims to invoke scientific and technological development of the model systems proposed during that ideation competition. Technological breakthroughs in this arena could allow researchers and physicians to better understand, diagnose, and treat retinal diseases.

The total prize purse for this 2-Phase Challenge is up to $1,000,000. Up to 6 winners will be awarded up to $100,000 each at Phase 1. Phase 2 will have up to 3 winners and the prize purse will total $400,000 plus any Phase 1 prize money that was not awarded for Phase 1. Additional teams may be recognized with non-monetary awards.

For full details about eligibility requirements, competition rules, and deadlines for submissions, please consult NEI's 3-D ROC Challenge Details page.

Background

Around the world, an estimated 285 million people are visually impaired; of these, 39 million are blind. In many cases, blindness and vision loss are the result of retina-damaging diseases that, if better understood, could be treated or have interventions applied to stop degeneration or provide protection to remaining viable cells. One limitation in furthering retinal research is that eye tissue is not readily available to study disease processes and test new therapies. However, retina biology researchers have developed methods to grow 3-D retina models in vitro from induced pluripotent stem cells (iPSC) and human embryonic stem cells (hESC). Current protocols vary in their strengths and limitations, but none can robustly recapitulate the complexity and functionality of the retina. In this Challenge, NEI seeks 3-D human retina organoid prototypes that are physiologically relevant. Such model systems could be transformational for vision research and regenerative medicine. New models could be used for applications such as understanding eye development, studying retinal biology, modeling diseases, identifying and testing treatments, and serving as a tissue source to use in transplantation. In this Challenge, solution(s) should yield reproducible, retina organoid models that represent the complexity, structure, and function of the human retina and are amenable for use in either modeling diseases or high-content screening.
Submissions Requested

Solutions must show publication-quality data demonstrating:
  • A 3-D human retina organoid system that mimics the physiological and morphological features of the in vivo biology, consists of the major retina cell types (rod and cone photoreceptors, horizontal, bipolar, amacrine, and ganglion cells and Muller glia) with appropriate lamination and synaptic organization, and represents their biological functions and interplay. Components (neurons, retinal pigment epithelium [RPE], glia) may be produced separately or dissociated and recombined (1) if protocol is driven by a valuable biological question and (2) if in the process of re-assembly, specific functions/roles of cell types are delineated. Three-dimensional assembly may be achieved using various approaches, for example through self-organization that recapitulates natural development ( true organoid ) or through bioengineering with scaffolds, bioprinting, and/or microfluidic apparatuses.
  • Retina organoids that are generated entirely from human cells (e.g. derived from iPSCs, hESCs , multipotent cells, or adult cells subjected to a combination of transdifferentiation/reprogramming methods). Please note that stem cells must adhere to the NIH Guidelines for Human Stem Cell Research Policy.
  • Modeling and treating retinal disease, or testing and developing drug (i.e., high content screening) therapies (for details, see Evaluation Criteria 4 below).
Explants are not of interest for this Challenge. Tissue-on-a-chip systems that use cells grown in 2-D co-culture and do not fully represent the structure, morphology, and function of the human retina are also not of interest. However, creative approaches that incorporate use of microfluidics or perfusion to enhance culture or extend duration of survival for 3-D organoid systems are acceptable.

Reviewers will be asked to use the following criteria when evaluating whether (in the form of results, graphs, images, etc.) a prototype 3-D human retina organoid meets evaluation criteria:
  • Significant advances over currently available protocols in areas such as duration of culture, yield, and maturity/differentiation of all cell types in appropriate numbers and ratio.
  • Potential impact on understanding the biology of the retina.
EVALUATION CRITERIA 1: Impact and Innovation
Solutions will be evaluated for creativity and originality of designs. An innovative approach may be novel, groundbreaking, or paradigm-shifting, or a creative application of existing approaches. For Phase 1 submissions, the approach should also be feasible; i.e., have a high likelihood to succeed in meeting or exceeding the scientific evaluation criteria NEI has defined. Overall, the solution should provide a novel solution to building a 3-D human retina that meets the desired scientific criteria (structure, function, morphology).

EVALUATION CRITERIA 2: Cell Type, Structure, and Function
Solutions will be evaluated for establishment of a human PSC-derived in vitro retina model system that resembles the morphology of a healthy-native retina and is viable through formation of photoreceptor outer segments and/or long-term survival of retinal ganglion cells with extension of axonal processes.

EVALUATION CRITERIA 3: Reproducibility, quality control, and standardization
Assessment of inter/intra-laboratory utility, transferability, and reproducibility, with conclusive evidence that organoid prototype is based on a reproducible protocol and the protocol produces a relatively standardized product.

EVALUATION CRITERIA 4: Endpoint assay-specific goals (must address one category)
BIOLOGY/DISEASE MODELING (note: NEI is agnostic to which disease is chosen, as long as technology is developed to robustly recapitulate the disease):
A. Does the organoid prototype demonstrate improvement in faithful biological complexity (e.g. macula, multiple cell subtypes present in physiologically similar ratios, etc.)?
B. Does the model recapitulate some aspect of disease phenotype in one or more assays?
C. Viability and scalability: If grown at one organoid/well, are 90% of organoids in a plate viable, as shown by random sampling in five wells across a dish? For how long are morphological and functional features maintained? Are methods that increase the production (e.g., many dozens) of organoids and/or allow the distribution of well-characterized organoids presented to enable multiple organoids to be compared in the same experiment?
D. Is therapeutic intervention to treat the disease modelled with 3-D retina organoids (e.g. via gene editing, small molecules, cell replacement, etc.) demonstrated?

HIGH CONTENT SCREENING:
A. Are retina organoid prototypes amenable to high content screening, which may include high content imaging, drug validation/toxicology, or functional genomic screening (e.g. does not include materials known to show strong compound adsorption)?
B. Does the model recapitulate known retina toxicities based on morphological and functional readouts?
C. Scalability and portability: Are organoids grown at medium throughput (e.g., in a 96-well plate) robust? When grown at one organoid/well, are 90% of wells in a plate viable, as shown by random sampling in five wells across a dish? For how long are morphological and functional features maintained? Are methods to mass-produce (e.g., 100s) organoids such that multiple plates can be compared in the same experiment included?
Submitting a Response

To register and submit for this Challenge, Solvers may access the registration and submission platform www.challenge.gov and search for "NEI 3-D Retina Organoid Challenge 2020."

For full details about eligibility requirements, competition rules, and deadlines for submissions, please consult NEI's 3-D ROC Challenge Details page.

Inquiries

Please direct all inquiries to:

Steven Becker, PhD
National Eye Institute (NEI)
Telephone: 301-496-2234
Email: steven.becker@nih.gov