The overall purpose of this funding opportunity announcement (FOA) is to invite applicants from multidisciplinary research teams to develop a community-based resource of microbial data associated with the resident ocular microbiome of healthy individuals. The data include factors microbial communities elaborate that impact human physiology. This announcement will support research projects designed to: delineate and characterize core ocular microbial constituents in the front of the eye; understand their immune and neuro interactions and contributions to the maintenance of homeostasis; and integrate microbiome, omics, and clinical data to determine profiles that promote health of the ocular surface. The front of the eye or anterior segment includes the ocular surface, cornea, iris, ciliary body, conjunctiva, lens, eyelids, and periocular skin.
The National Eye Institute (NEI) Anterior Segment Initiative (ASI) was launched in 2019 to address challenges in understanding and treating disorders of the anterior segment of the eye. The ASI is developing workshops and events to explore the role of the immune system in the anterior segment, and how the immune system interacts with ocular nerves in disease and in healthy aging. The ocular microbiome is one component of this initiative. An executive summary of a recent NEI-sponsored workshop addressing challenges in studying the ocular surface microbiome can be found here: NEI Microbiome Report.
The National Institutes of Health (NIH) Human Microbiome Project (HMP) characterized several ecological niches of the human body, most notably in the nasal passages, oral cavity, skin, gastrointestinal tract, and the urogenital tract. Results from this project showed that the diversity and abundance of each habitat’s signature microbes vary widely among healthy subjects. Metabolic reconstruction of metagenomic data demonstrated that the core biochemical and metabolic pathways are relatively stable among individuals despite variation in community structure and ethnic/racial background. The HMP has also generated resources and leveraged technologies that facilitate characterization of the human microbiota and further our understanding of how the microbiome impacts human health and disease. These include DNA sequencing such as 16S rRNA gene-based amplicon sequencing and metagenomic approaches, software programs such as Decontam R statistical methods that are used to identify and visualize contaminating DNA features, as well as the use of bioinformatics to integrate large microbial, omics and clinical datasets.
Recent data suggest the existence of a resident ocular microbiome—one that may play a protective role in corneal infections. Studies are being undertaken to explore the gut, oral and ocular microbiome’s role in various eye conditions including dry eye, meibomian gland dysfunction, endophthalmitis, uveitis, blepharitis, diabetic retinopathy, age related macular degeneration and contact lens wear. But explorations of ocular microbiome dysbiosis have been stymied by the lack of robust data on the phylogenetic and taxonomic composition including diversity and abundance of the microbiota that exist in a healthy eye. Likewise, the molecular underpinnings of noted associations between the microbiome and ocular immune modulation and homeostasis remain largely unexplored.
Delineating the range of structural and functional configurations of a healthy population’s resident microbial community will pave the way for broader studies of the epidemiology, ecology, and translational applications of the human ocular microbiome. Knowledge of the diversity and abundance of resident microbiota is critical to advancing the development of microbiome-based interventions for prevention and treatment of eye diseases.
This announcement invites applications proposing to develop a community-based resource of microbial communities and factors they elaborate that are associated with the resident ocular surface microbiome of healthy individuals. As a result, discovery-based projects that are not hypothesis driven may be appropriate.
Characterization of the anterior segment’s microbiome and microbial strains and interactions that modulate host physiology will require the coordinated efforts of investigators with diverse sets of expertise including clinical vision research, microbiology, high-throughput genetic sequencing, generation of multi-omics data, bioinformatics, and systems for culturing cells and validating microbes. This FOA accordingly uses the U24 mechanism to invite applications from multidisciplinary teams of investigators to create a community research resource.
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