<b>Myeloid cell protein tyrosine phosphatase 1B (PTP1B) drives retinal neurodegeneration in diabetic mice</b>

<p dir="ltr"><a href="" target="_blank">Diabetic retinopathy (DR) is the leading cause of vision loss in the working age population with public health economic implications worldwide. Systemic inflammation and leukocyte activation are early events in diabetes, while microglial activation, neuroinflammation, and retinal neurodegeneration are early events in DR. Protein tyrosine phosphatase 1B (PTP1B) plays a complex role in monocyte / macrophage activation which may impact DR. We therefore investigated the role of myeloid cell-specific PTP1B using LysM^cre-PTP1B fl/fl (LysM-PTP1B) transgenic mice, as well as pharmacological inhibition with a PTP1B inhibitor, MSI-1436, in the early stages of DR. Mice were rendered diabetic for six weeks using anomer-equilibrated streptozotocin (STZ). Retinal changes were evaluated by histology and immunohistochemistry, and systemic leukocyte activation by flow cytometry. Mitochondrial function in high glucose-challenged, cultured bone marrow-derived macrophages (BMDMs) from LysM-PTP1B and MSI-I436-treated mice was determined <i>in vitro</i>. Both myeloid cell-specific depletion and pharmacological inhibition of PTP1B prevent STZ-induced retinal neurodegeneration, development of acellular retinal capillaries, as well as microglial and systemic leukocyte activation without altering the development of diabetes. <i>In vitro</i>, inhibition of PTP1B prevented high glucose-induced mitochondrial dysfunction in BMDMs. We conclude that inhibition of PTP1B prevents DR by decreasing myeloid cell-driven inflammation and PTP1B represents a therapeutic target for prevention DR.</a></p>