Background. Transient receptor potential (TRP) channels are a superfamily of ion channels that serve as polymodal cell sensors for diverse chemical and physical stimuli in numerous cell types. Much of our knowledge on the role of TRP channels in the pathophysiology of ocular surface diseases is incomplete and there is no Literature on conjunctival expression of TRPs in the diseased human conjunctiva. Understanding TRP function and polymodal regulation associated to pain and neuroinflammation of the ocular surface represents a challenging goal.
Purpose. The present project aims to evaluate the expression of TRPV1/V4 and TRPM8 in the conjunctiva of patients diagnosed with Sjogren's syndrome (SS), neurotrophic keratitis (NK) and vernal keratoconjunctivitis (VKC) compared to a group of healthy subjects, and correlations with clinical parameters.
Design. Prospective, cross-sectional study.
Methods. Thirty patients diagnosed with ocular surface disorders including 10 patients diagnosed with SS, 10 patients diagnosed with NK and 10 patients diagnosed with VKC, and 10 healthy subjects will be subjected to conjunctival impression cytology to evaluate the protein expression of TRPV1/V4 and TRPM8. Participants will also undergo complete clinical and instrumental ophthalmological evaluation including corneal confocal microscopy, in order to collect functional and morphological parameters.
Results. Levels of TRPV1/4 and TRPM8 will be evaluated in the collected conjunctiva epithelium samples. Correlation analyses between TRPs profiles observed in the conjunctival samples and clinical parameters will be evaluated. Conjunctival characterization of TRPs in SS, NK and VKC con represent an innovative and indispensable area of interest to clarify the pathogenesis of these diseases associated to pain, dryness, and inflammation of the ocular surface. This study will offer potential biomarkers of ocular surface disease as well as promising targets for the development of therapeutics.
The expression of TRPV1/4 and TRPM8 in the conjunctiva of SS, NK and VKC patients can represent a valid contribution in clarifying the pathogenesis of these diseases, all showing ocular surface inflammation, impaired tear film production and neurosensory abnormalities. The complete clinical and instrumental ophthalmological evaluation will offer the opportunity to collect clinical, morphological and functional data to be correlated with TRPs¿ levels in the conjunctiva. Only a few recent preclinical studies investigated the role of TRPs in ocular surface diseases [12]. This is the first study in Literature that aims to evaluate the expression level of TRPs in the diseased conjunctiva. Specifically, the involvement of TRPs will be assessed in the conjunctiva of patients diagnosed with SS, NK and VKC, challenging and potentially blinding diseases of the ocular surface. Our results are expected to have a major impact on basic research, clinical knowledge and pharmaceutical industry. The results of the present project will advance knowledge on clinical science in ocular physiopathology and disease treatment. Specifically, the present study will contribute to the identification of novel biomarkers
for ocular surface diseases and will offer viable perspectives on modulation of TRPs as an attractive therapeutic target for the treatment of neuroinflammation and pain of the ocular surface.
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