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TitleP2X7, a new therapeutic target in inflammatory eye diseases
PurposeThe study of new therapeutic targets in the management of inflammatory eye diseases is essential. Among the potential candidates, the purinergic receptor P2X7 has generated increasing interest since the discovery of its involvement in inflammatory responses in the central nervous system. Our aim was to assess the impact of invalidating the expression of P2X7 in various mouse models at the level of CD4+ effector T lymphocytes, regulatory T lymphocytes and retinal microglia/mononuclear phagocytes, involved in the immune response during experimental autoimmune uveoretinitis (EAU).
MethodsWe used different lines of mice (P2X7-/-, FoxP3CreERT2P2X7lox and CX3CR1CreP2X7lox respectively) with a C57Bl/6 genetic background in which we induced EAU either by immunization against IRBP or by adoptive transfer of activated T lymphocytes specific for IRBP from WT mice. They were then examined by a regular eye fundus imaging and optical coherence tomography. At the acute or remission phase of the disease, they were sacrificed to harvest their retina, spleen and lymph nodes which we then analysed by flow cytometry to determine the expression of P2X7 and the proportion of each cell of interest in these organs.
ResultsWe did not find any significant effect of P2X7 inhibition in effector or regulatory CD4+ T cells on disease induction or severity. However, inhibition of P2X7 expression in retinal microglia/mononuclear phagocytes significantly reduced the severity of EAU.
ConclusionThe harmful pro-inflammatory role of P2X7 in mononuclear phagocytes infiltrating the retina during EAU makes the latter the most relevant therapeutic target.
Conflict of interestNo
Authors 1
Last namePIERRE
Initials of first name(s)M
DepartmentOphthalmology
CityParis
CountryFrance
Authors 2
Last nameTOUHAMI
Initials of first name(s)S
DepartmentOphthalmology
CityParis
CountryFrance
Authors 3
Last nameBODAGHI
Initials of first name(s)B
DepartmentOphthalmology
CityParis
CountryFrance
Authors 4
Last nameDELARASSE
Initials of first name(s)C
DepartmentImmunology
CityParis
CountryFrance