During the pathogenesis of retinitis pigmentosa (RP), the roles of retinal microglial cells after activation have not been fully elucidated. Herein, experimental RP was induced in Sprague Dawley rats by intraperitoneal injection of N-methyl-N-nitrosourea (MNU) at 50 mg/kg, and the effects of MNU on the retinas were evaluated, respectively, by retinal histology and electroretinography recordings at serial time points. Time-dependent and gradual loss of photoreceptor cells, disrupted arrangement of the outer nuclear layer (ONL), and significant reductions in both a-wave and b-wave amplitudes were observed. Morphology changes were observed in retinal microglial cells; meanwhile, with time, the number of lba1-positive microglia and their infiltration into the ONL gradually increased. Furthermore, physical interaction of microglial-Muller cell processes following microglial activation was observed after MNU injection. In addition, Muller cells increased CX3CL1 secretion, enhanced microglial cell migration, and upregulated the CX3CR1 expression of the latter. Our observations implied that, during the pathogenesis of RP by MNU, microglial cells exhibit a prominent morphology change and Muller cells can induce activated microglia infiltration by increasing secretion of the chemotaxis factor, CX3CL1, and promoting the migration of retinal microglial cells. This novel finding highlights a potential therapeutic target aimed at regulating the microglial response.
[1]Fudan Univ, Sch Basic Med Sci, Dept Anat Histol & Embryol, Shanghai, Peoples R China;
[2]Sch Basic Med Sci, Dept Integrat Med & Neurobiol, Shanghai, Peoples R China;
[3]Fudan Univ, Eye & ENT Hosp, Shanghai Med Coll, Shanghai, Peoples R China;
[4]Shanghai Jiao Tong Univ, Sch Med, Dept Radiat Oncol, Shanghai Peoples Hosp 9, Shanghai, Peoples R China;
[5]Key Lab Med Imaging Comp & Comp Assisted Interven, Shanghai, Peoples R China
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