{"id":"https://openalex.org/G3855754276","display_name":"Neuroimmune pathophysiological mechanisms of ocular surface disease","description":"Dry eye is a highly prevalent ocular surface disorder in which a localized CD4+ T cell response and corneal nerve dysfunction are core pathophysiological mechanisms. Both aspects of the disease develop concomitantly in murine models but their connection is unclear. Our preliminary data suggests that the pathogenic immune response is linked to corneal nerve damage and that transient receptor potential vanilloid 1 (TRPV1) signaling promotes nerve-initiated (neurogenic) inflammation. Neurodegeneration is induced by TRPV1 overactivation and leads to neurogenic inflammation in other settings. Therefore, we hypothesize that 1) CD4+ T cells damage corneal nerves in dry eye; and that 2) increased TRPV1 activation promotes nerve damage and neurogenic inflammation, thus worsening the disease (vicious cycle). We will explore the first possibility by using T cell-deficient mice and adoptive transfer of T cells; and the second, with TRPV1-deficient mice and a unilateral surgical model of dry eye in which neurogenic inflammation manifests in the opposite eye. We will explore corneal nerve morphology and function, the possible autoimmune origin of neural changes, and the accompanying T cell response in these models. These findings could serve to develop a dry eye treatment that addresses corneal nerve damage and its associated neuropathic pain.","funder_award_id":"221859","funder":{"id":"https://openalex.org/F4320311904","display_name":"Wellcome Trust","doi":"10.13039/100010269"},"funded_outputs":["https://openalex.org/W3133345685","https://openalex.org/W3150471588","https://openalex.org/W4220728538","https://openalex.org/W4285606169","https://openalex.org/W4293109509","https://openalex.org/W4309213922","https://openalex.org/W4319065984","https://openalex.org/W4391542153","https://openalex.org/W4401834256","https://openalex.org/W4403587407"],"funded_outputs_count":10,"parent_awards":[],"sub_awards":[],"sub_awards_count":0,"amount":339911.06,"currency":"GBP","amount_usd":465701.28,"amount_usd_basis":"daily_rate","recipients":[],"recipient_countries":[],"recipient_regions":[],"research_scope":{"is_research":true,"basis":"funder_default","tier":1},"funding_type":"fellowship","funder_scheme":"Immune System in Health and Disease","start_date":"2021-02-01","end_date":"2026-01-31","start_year":2021,"end_year":2026,"landing_page_url":"https://europepmc.org/grantfinder/grantdetails?query=pi:\"%7BDr%7D%7BGalletti%7D%7BJeremias%7D%7BJ%7D\" gid:\"221859\" ga:\"Wellcome Trust\"","doi":"https://doi.org/10.35802/221859","provenance":"crossref_work","lead_investigator":{"given_name":"Jeremias","family_name":"Galletti","orcid":"https://orcid.org/0000-0002-5118-2540","role_start":null,"affiliation":{"name":"Academia Nacional de Medicina","country":"AR","ids":[{"id":"https://ror.org/05k2xsz75","type":"ROR","asserted_by":"publisher"}]}},"co_lead_investigator":null,"investigators":null,"works_api_url":"https://api.openalex.org/works?filter=awards.id:G3855754276","primary_topic":{"id":"https://openalex.org/T10997","display_name":"Ocular Surface and Contact Lens","score":0.9914,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10997","display_name":"Ocular Surface and Contact Lens","score":0.9914,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"institution_awarded":[{"id":"https://openalex.org/I14429277","display_name":"Academia Nacional de Medicina","ror":"https://ror.org/05k2xsz75","country_code":"AR","type":"nonprofit","lineage":["https://openalex.org/I14429277"]}],"updated_date":"2026-10-16T03:01:01.000Z","created_date":"2021-11-08T09:45:42.000Z"}