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Fengyang Lei, Claes H Dohlman, James Chodosh, Eleftherios I Paschalis; Corneal injury causes retinal inflammation. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2529.
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© ARVO (1962-2015); The Authors (2016-present)
In prior studies we showed that corneal alkali burn leads to retinal damage by a mechanism that is purely inflammatory. Clinical data suggest that ocular surgery, such as keratoprosthesis implantation, may increase glaucoma risk despite efforts to control intraocular pressure. In this study we use a murine model to assess the effect of various types of corneal surgical injuries in retinal inflammation and immune cell activation.
Three corneal injury models were used: 1. Corneal suture (penetrating), 2. Penetrating keratoplasty (PK), 3. PK with lensectomy. Retinal inflammation was assessed with quantitative PCR for tumor necrosis factor alpha (TNF-α), TNF receptor 1 (TNFR1), TNFR2, interleukin 1β (IL-1β), and IL-6. Blood-derived monocyte infiltration in the retina was assessed using a bone marrow chimera model, in which CX3CR1GFP/+::CCR2RFP/+ bone marrow cells were grafted into C57BL/6 mice. Cell infiltration was quantified using confocal microscopy.
All types of corneal surgical injuries caused prompt infiltration of blood-derived CCR2+ CX3CR1+ monocytes into the retina and upregulation of inflammatory genes within 24 hours. The degree of retinal inflammation correlated with the severity of the ocular injury. The fold increase of retinal inflammatory genes for corneal suture, PK, and PK + lensectomy was as follows: TNF-α: 5, 10, 40; TNFR1: 4, 6, 4; TNFR2: 4, 6, 6; IL-1β: 13, 35, 207; IL-6: 14, 108, 56, respectively (Bonferroni adjusted p< 0.05 for all genes). Uninjured mice had no infiltration of blood-derived CCR2+::CX3CR1+ cells and normal inflammatory gene levels.
In a mouse model, corneal surgical injury can cause retinal inflammation and infiltration of blood-derived monocytes. The degree of inflammation correlates with severity of the injury. Although preliminary, this study supports the existence of an immunological connection between the anterior and posterior segment, which may explain in part the increased incidence of glaucoma in patients with severe ocular injuries. Further work is necessary to understand the consequences of inflammation for the retinal neurons.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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