The broad goal of the proposed research is to elucidate the mechanisms involved in vision - thus enabling correction of these when become compromised. In this endeavor, studies are proposed on how the cornea (the outermost structure of the eye) protects itself from damage. A major source of protection - and the focus of the proposed studies - is corneal sensory innervation. In the cornea, the sensory nerves transduce a variety of mechanical, thermal and chemical stimuli to sensations of pain, thereby protecting the cornea through avoidance of these painful, and potentially harmful stimuli. In addition, the nerves produce molecular factors that maintain a healthy cornea. Therefore, the loss of corneal nerves - through trauma, surgery or infection - can lead to damage, which in the most severe cases can require corneal transplant. The proposed studies are designed to increase the understanding of how corneal innervation is regulated, both during normal development and following refractive surgery. Thus, the information obtained will potentially be applicable to maintaining normal innervation, and promoting reinnervation following conditions in which innervation is compromised. One area that will be of study is based on previous work, and preliminary results that have uncovered a novel cell type of the corneal epithelium (which is the outermost tissue layer of the cornea). This cell type has unique properties that suggest an involvement in innervation - including attracting nerves to the corneal surface, which is the primary location for sensory perception. To further understand these cells and their function(s) in corneal innervation - the genes that they utilize at various steps in innervation will be determined, and these will be compared to other cells of the cornea. Also, the functional roles of these genes in normal corneal innervation will be determined using in vivo and in vitro approaches. And, the results of these studies on normal developmental innervation will be compared with reinnervation following refractive laser surgery (in adult chickens). The other area of study will involve a previously-undetected barrier to molecular diffusion, located at the outer border of the cornea. Preliminary results suggest that, during corneal development this barrier functions to spatially localize developmental signals to the cornea - such as those required for normal innervation. Proposed studies will involve determining the mechanism through which this barrier restricts signaling, and how this may influence corneal innervation. Together, the successful completion of these two areas of investigation should increase the understanding of corneal innervation, and thus will promote the long-term goal of preserving normal vision.

Public Health Relevance

Maintaining a healthy cornea is vital for normal vision. This requires proper innervation, as the corneal nerves provide protection and support for the cornea. The ultimate goal of the proposed research is to determine the mechanisms by which corneal nerves protect the cornea and thereby preserve sight.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (BVS)
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Mckie, George Ann
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Tufts University
Anatomy/Cell Biology
Schools of Medicine
United States
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Talbot, Christopher J; Kubilus, James K (2018) Developmental analysis of SV2 in the embryonic chicken corneal epithelium. Exp Eye Res 172:137-143
Kubilus, James K; Zapater I Morales, Carolina; Linsenmayer, Thomas F (2017) The Corneal Epithelial Barrier and Its Developmental Role in Isolating Corneal Epithelial and Conjunctival Cells From One Another. Invest Ophthalmol Vis Sci 58:1665-1672
Canner, James P; Linsenmayer, Thomas F; Kubilus, James K (2014) Developmental regulation of trigeminal TRPA1 by the cornea. Invest Ophthalmol Vis Sci 56:29-36