Project Details
Abstract
Being the 4th cause of blindness globally, corneal visual impairment encompasses a wide variety of infectious and inflammatory eye diseases that cause corneal scarring, which ultimately leads to vision loss. Persistent corneal epithelial defect (PCED) is one of the major causes leading to corneal blindness in many corneal disorders. PCED is associated with several clinically significant morbidities, including infectious keratitis, corneal scarring, melting, perforation, endophthalmitis and phthisis bulbi. Diabetic keratopathy is one of the major risk factors for PCED and the corneal wounds secondary to corneal abnormalities in diabetic patients are usually refractory to conventional treatment and may lead to neurotrophic corneal ulceration, secondary infection and loss of eyesight.
Corneal epithelial wound healing involves a cascade of complex processes including cell death, migration, proliferation and extracellular matrix remodeling. Accumulating evidence has suggested that cytokines / growth factors deficiencies and impaired downstream signaling pathways are associated with delayed corneal epithelial wound healing. Despite that biological tear substitutes and amniotic membrane transplantation are effective on promoting corneal epithelial healing; however, there are currently no specific treatments for PCED in eyes with neurotrophic keratopathy. A large body of evidence has demonstrated that negative pressure wound therapy (NPWT) can effectively reduce the size of the wound. Recently, this laboratory finds that (1) negative pressure promotes corneal epithelial wound healing in a human corneal epithelial cell line; (2) negative pressure facilitates migration of human primary corneal epithelial cells; (3) attenuated expression of intercellular adhesion molecules E-cadherin and zonula occludens-1 (ZO-1) in response to negative pressure treatment; (4) p120, a member of armadillo repeat containing proteins, undergoes nuclear translocation under a negative pressure environment. However, the effects of NPWT on corneal wound healing and the underlying molecular mechanisms remain elusive.
Cell shape has been well established to govern its behavior and the cytoskeletal change generates organizational guidance cues for cells. This project hypothesizes that negative pressure will promote corneal epithelial wound healing via generating a complex mechanical environment at the wound surface. The resultant cell deformations after negative pressure lead to cellular migration, proliferation, and differentiation. It is also possible that negative pressure stimulates neural growth and neuropeptide expression, further promotes corneal epithelial wound healing. However, the candidate proteins and mechanisms underlying negative pressure should be carried out. Therapeutic strategy targeting at negative pressure and related candidate cytokines / growth factors will be beneficial for PCED repair. Therefore, the specific aims of this project are to study the effects of negative pressure on corneal epithelial cells. A cell culture platform will be used to clarify the mechanisms underlying negative pressure-induced signaling. Proteomic study will be utilized to dig out the target proteins after negative pressure application. Finally, chemically-induced diabetic animal model will be used to explore the therapeutic possibility of negative pressure alone or in combination with candidate proteins for accelerating corneal wound healing. Further study in the next few years will shed light on the molecular mechanisms underlying negative pressure-related corneal epithelial proliferation and migration and hopefully discover novel targets for the treatment of PCED.
Project IDs
Project ID:PC10901-0337
External Project ID:MOST108-2314-B182-049-MY3
External Project ID:MOST108-2314-B182-049-MY3
Status | Finished |
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Effective start/end date | 01/08/20 → 31/07/21 |
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