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. 2022 Dec 10;7(2):144–153. doi: 10.1177/24741264221135799

Figure 1.

Figure 1.

MTX and adenosine signaling. Extracellular signals from retinal detachment stimulate an immune cascade and a proliferation signal of RPE cells and RGCs important in PVR pathogenesis. 10 MTX blocks the enzyme inosine monophosphate synthase (also known as aminoimidazole carboxamide ribonucleotide transformylase), resulting in elevated intracellular AICAR levels, leading to increased intracellular adenosine. 8 Adenosine is transported out of the cell by the extracellular nucleoside transporter, where it might act on G-protein coupled receptors and/or be transported intracellularly to inhibit proinflammatory cytokine release in immune cells. MTX also blocks thymidylate synthase and reduces proliferation of RPE cells and RGCs in the formation of PVR. Finally, MTX inhibits dihydrofolate reductase.

Abbreviations: AICAR, amidoimidazole carboxamide ribonucleotide; MTX, methotrexate; PVR, proliferative vitreoretinopathy; RGCs, retinal glial cells; RPE, retinal pigment epithelium.