Research

Corneal Wound Healing

The cornea is an optically clear tissue that forms the front surface of the eye, and accounts for nearly two-thirds of its refractive power. The corneal stroma, which makes up 90% of corneal thickness, is a highly organized structure consisting of collagen lamellae with specific packing and spacing that is critical to maintenance of corneal transparency. Corneal stromal cells (keratocytes) reside between the collagen lamellae, and are responsible for secreting extracellular matrix (ECM) components required to maintain normal corneal structure and function (i.e. transparency). Because it is exposed, the cornea is susceptible to infection, physical and chemical injuries; it is also the target of many vision correction procedures.

Stromal keratocytes play a central role in mediating the corneal response to lacerating injury, chemical injuries or surgical procedures. During wound healing, quiescent corneal keratocytes surrounding the area of injury generally become activated, and transform into a fibroblastic repair phenotype. In certain wound types, fibroblasts further differentiate into myofibroblasts, which generate stronger forces and synthesize a disorganized fibrotic ECM. Cellular force generation and fibrosis can alter corneal shape and/or reduce corneal transparency, thereby reducing visual acuity.

In addition to fibrosis which develops on top of the wound bed, most vision correction procedures induce keratocyte death beneath the laser-treated area.  Stromal cell death can also be induced by toxic injury, as well as UV cross-linking (CXL) of the cornea in keratoconus patients. Ideally, repopulation following these insults should occur via intra-stromal migration of keratocytes from the surrounding stromal tissue, without generation of strong contractile forces that could disrupt the collagen architecture and lead to vision loss.

Our lab develops and applies high resolution imaging and image processing approaches to better understand and potentially modulate these healing responses. Specifically, we use in vivo confocal microscopy to assess stromal keratocyte differentation, patterning and activation in response corneal injury, surgery or disease. We also use 3-D confocal and multiphoton imaging of corneal tissue ex vivo to assess the expression and localization of specific proteins associated with wound healing (using fluorescent labeling) as well as changes in extracellular matrix organization (using second harmonic generation imaging).1,2

References

  1. Petroll WM, Kivanany PB, Hagenasr D, Graham EK. Corneal Fibroblast Migration Patterns During Intrastromal Wound Healing Correlate With ECM Structure and Alignment. Invest Ophthalmol Vis Sci. 2015 Nov;56(12):7352-61.

  2. Kivanany PB, Grose KC, Tippani M, Su S, Petroll WM. Assessment of Corneal Stromal Remodeling and Regeneration after Photorefractive Keratectomy. Sci Rep. 2018 Aug 22;8(1):12580.