Ocular Surface Innervation from Cell Types to Circuit Functions (U01 Clinical Trial Not Allowed) | RFA EY 21 004

Opportunity Information: Apply for RFA EY 21 004

The NIH funding opportunity titled "Ocular Surface Innervation from Cell Types to Circuit Functions (U01 Clinical Trial Not Allowed)" (RFA-EY-21-004) supports coordinated, team-based basic research aimed at mapping and explaining how the front surface of the eye is wired and how that wiring drives sensation, pain signaling, and protective reflexes such as tearing. The core scientific focus is ocular surface innervation, starting at the cornea and extending through the relevant neural pathways that encode normal sensation as well as pain, and that connect sensory input to downstream circuit outputs like lacrimation. The FOA is positioned as foundational biology that can clarify what goes wrong in clinically important conditions, particularly neuropathic ocular pain and dry eye disease, and in doing so set the stage for later translational and clinical work on the anterior segment of the eye. Because the mechanism is U01, the intent is not just to fund isolated projects, but to foster coordinated efforts where NIH involvement and collaboration are part of the structure of the award.

A central feature of the announcement is its insistence on an integrated, systems-style approach at multiple levels of analysis. Applicants are asked to interrogate ocular surface innervation across three complementary dimensions: morphologic, molecular, and functional. Morphologic work typically refers to defining anatomy and structure, such as identifying which nerve fiber types innervate the cornea and ocular surface, how they branch, where they terminate, and how they connect to upstream or downstream nodes in the pathway. Molecular work focuses on cell types and their defining signatures, such as gene expression programs, receptor and ion channel profiles, neurochemical markers, and molecular pathways that differentiate sensory neuron subtypes or supporting cells and predict what kinds of stimuli they detect and how they respond to injury or disease-like perturbations. Functional work addresses what these components actually do, for example how specific afferent populations encode mechanical, chemical, or thermal stimuli; how those signals propagate into pain-related circuits; and how they engage reflex arcs controlling tearing. The FOA makes clear that competitive projects should combine at least two of these levels in a tightly linked way, and that the strongest applications will integrate all three so that structure, molecular identity, and function inform one another rather than being studied in parallel without connection.

The program is explicitly designed for collaborative, multidisciplinary teams with complementary expertise, reflecting the complexity of connecting cell types to circuits and behaviors. In practice, that means proposals are expected to bring together investigators who can jointly cover high-resolution anatomy, modern molecular profiling, and rigorous functional measurements, then integrate those outputs into a coherent picture of the system. The emphasis is on comprehensive delineation of the pathway from corneal sensation through pain circuits and tearing reflexes, so teams that can connect peripheral sensory endings to central processing and effector responses are aligned with the stated goals. Importantly, the FOA is labeled "Clinical Trial Not Allowed," which signals that the funded studies must remain in the basic or preclinical domain rather than testing clinical interventions in humans.

From an administrative standpoint, this is a discretionary, health-related cooperative agreement offered by the National Institutes of Health, with the activity code U01 indicating a cooperative research project where NIH anticipates substantial programmatic involvement. The Catalog of Federal Domestic Assistance (CFDA) number listed is 93.867. The opportunity was created on 2021-12-10 and had an original closing date of 2022-03-07. The source description does not specify an award ceiling or the expected number of awards, indicating those details were either not provided in the excerpt or were to be defined elsewhere in the full FOA.

Eligibility is broad and includes many types of U.S. organizations and several categories of international or special-status entities. Eligible applicants include state, county, city or township, and special district governments; independent school districts; public and state-controlled and private institutions of higher education; federally recognized Native American tribal governments; tribal organizations other than federally recognized tribal governments; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and other organizations. The FOA also highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, U.S. territories or possessions, faith-based or community-based organizations, eligible federal agencies, regional organizations, and non-U.S. (foreign) entities. This breadth is consistent with the emphasis on building multidisciplinary collaborations and enabling participation across different institutional types and geographies.

In plain terms, this opportunity is aimed at teams that can produce an integrated map and mechanistic understanding of how ocular surface nerves are built, how they are molecularly specified, and how they function as part of larger neural circuits that generate sensation, pain, and tearing. The long-term value is that by establishing a clearer baseline of normal organization and signaling, the field will be better positioned to explain and eventually treat pathological states like chronic ocular pain and dry eye disease, even though this particular FOA is focused on the preclinical groundwork rather than clinical testing.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Ocular Surface Innervation from Cell Types to Circuit Functions (U01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.867.
• This funding opportunity was created on 2021-12-10.
• Applicants must submit their applications by 2022-03-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA EY 21 004

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: