The Anterior Segment Initiative has funded eight research projects to explore the innervation of the eye’s surface. The collaborative projects will examine the molecular, morphological, and functional aspects of corneal pain and sensation, and tearing reflexes. Project findings will inform understanding of dry eye disease, neuropathic ocular pain, migraine, Sjogren’s syndrome, and other conditions that affect the anterior segment of the eye.
These projects bring together large, multidisciplinary teams of scientists, often from multiple institutions. Through this collaborative approach, NEI is supporting the development of new techniques, new resources, and unique datasets that will benefit the vision research field for years to come. NEI has committed over $50M to these projects over the next 5 years.
Mechanisms of pain and photophobia in migraine and dry eye (EY034680)
Sue Aicher and Catherine Morgans, Oregon Health Sciences University, and Tally Largent-Milnes, University of Arizona
Common conditions like dry eye disease and migraine, and procedures like refractive surgery, can lead to ocular pain and photophobia—pain and distress from bright light. A team led by Sue Aicher, Ph.D., will investigate how the ocular branch of the trigeminal nerve may influence these symptoms. Using rodent models, the team will explore molecular and cellular signals that disrupt feedback mechanisms between the trigeminal nerve and the cornea, retina and iris. The researchers hope to identify potential therapeutics for ocular pain and photophobia.
Understanding neural control of the ocular surface (EY034693)
Michael Jenkins, Carl Saab, Marcin Golczak, Rony Sayegh, Patricia Taylor, William Dupps, and David Wilson, Case Western Reserve University
A multidisciplinary team led by Michael Jenkins, Ph.D., will use an array of cutting-edge technologies to explore the molecular, cellular, and functional control of tear film production and the epithelial homeostasis of the cornea. These technologies will enable the team to visualize corneal nerve structure and signaling in animal models of dry eye disease, diabetes, and corneal infection. Additionally, they will explore connections to neighboring regions, including the trigeminal ganglion and glands in the eyelid. The team also plans to test nerve growth factor’s potential to ameliorate disease-related sensation and function abnormalities.
Central and peripheral mechanisms of corneal pain (EY034709)
Ian Meng, University of New England; Pedram Hamrah, Tufts University; and William Renthal, Harvard Medical School
A team led by Ian Meng, Ph.D., will examine the cellular and molecular properties of corneal nerves and how the corneal nerves respond to injury. Using rodent models, the team will use gene expression profiling, imaging, and functional studies to explore how corneal nerves become over-sensitized in acute and chronic injury models. They will also investigate the immune system’s role in corneal pain.
Differentiation of clinical phenotypes of inflammatory and neuropathic ocular pain conditions with morphologic measures and functional brain imaging (EY034686)
Eric Moulton, Joseph Ciolino, Deborah Jacobs, Scott Holmes, and David Zurakowski, Harvard University; and Anat Galor and Elizabeth Roy Felix, University of Miami
People with dry eye disease and Sjogren’s syndrome often have corneal inflammation along with neuropathic pain. A team led by Eric Moulton, O.D., Ph.D., will use technologies functional magnetic resonance imaging (fMRI) and in vivo confocal microscopy to examine patients’ immune system activity and corneal nerves. The team plans to generate objective clinical measures that can be used in future clinical trials testing potential therapeutics for neuropathic corneal pain.
Underpinnings of corneal innervation: anatomical, molecular, and functional studies of corneal sensory afferents in physiologic and pathologic states (EY034681)
Panteleimon Rompolas, Vivian Lee, Wenqin Luo, Hao Wu, and Long Ding, University of Pennsylvania
Panteleimon Rompalas, Ph.D., and a multidisciplinary team are investigating damage-induced molecular changes that occur in individual neurons. With a rodent model of dry eye disease, the team will pair artificial intelligence with high-speed nerve signal imaging to measure how nerve function aligns with an animal’s behavioral response. Their goal is to create baseline datasets to inform future studies.
Effects of cornea epithelial barrier disruption on the cornea trigeminal neural circuit (EY034692)
Stephen Pflugfelder, Rui Chen and Cintia De Paiva, Baylor College of Medicine; and Mary Ann Stepp, George Washington University
Corneal nerve ends closely integrate with the corneal epithelial layers. A team led by Stephen Pflugfelder, Ph.D., and collaborators will investigate how disruptions to the corneal epithelial barrier influence corneal nerve health. In a rodent model of dry eye disease, the team will test whether preserving the corneal epithelial barrier prevents corneal signaling cascades that cause nerve damage.
Blink, lacrimation, and nociception: precision mapping and integrated atlas generation of corneal trigeminal afferents (EY034687)
Daniel Saban, Sina Farsiu, Jadee Neff, and Victor Perez Quinones, Duke University, and Anna Matynia and Igor Spigelman, University of California, Los Angeles
A team led by Danial Saban, Ph.D., is exploring corneal nerves that control blinking and tear production. Using multi-color microscopy and gene expression analyses, they will establish the presence and arrangement of nerve types in rodent and human cornea. Pairing this information with machine learning and artificial intelligence-based analysis, the team seeks to understand the molecular and structural forces that maintain tear film.
Assessing how ocular surface nerves, immune cells, and epithelial cells communicate to encourage neuro-immune homeostasis (EY034711)
Anthony St. Leger, Daniel Kaplan, Harinder Singh, Brian Davis, Yun Hongmin, Robert Shanks, Jishnu Das, and William Hawse, University of Pittsburgh
A team led by Anthony St. Leger, Ph.D., is investigating corneal surface nerves at a system level. Using an unbiased approach, the team aims to generate large, publicly available datasets with molecular, cellular, and functional corneal nerve data. They will also use a system known as DREADD (Designer Receptor Exclusively Activated by Designer Drugs) to directly stimulate individual classes of neurons, exploring the role of each neuronal cell type in the cornea. Using machine learning, the group will develop models of corneal nerve cell interaction to study sensation, tear film maintenance, and other functions.