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.