Subject(s)
Autoimmune Diseases of the Nervous System/diagnosis , Lung Neoplasms/diagnosis , Optic Neuritis/diagnosis , Paraneoplastic Syndromes, Nervous System/diagnosis , Paraneoplastic Syndromes, Ocular/diagnosis , Retinitis/diagnosis , Small Cell Lung Carcinoma/diagnosis , Aged, 80 and over , Autoimmune Diseases of the Nervous System/etiology , Autoimmune Diseases of the Nervous System/prevention & control , Chemoradiotherapy , Diagnosis, Differential , Humans , Lung Neoplasms/complications , Lung Neoplasms/therapy , Male , Optic Neuritis/etiology , Optic Neuritis/prevention & control , Paraneoplastic Syndromes, Nervous System/etiology , Paraneoplastic Syndromes, Nervous System/prevention & control , Paraneoplastic Syndromes, Ocular/etiology , Paraneoplastic Syndromes, Ocular/prevention & control , Retinitis/etiology , Retinitis/prevention & control , Small Cell Lung Carcinoma/complications , Small Cell Lung Carcinoma/therapy , Treatment OutcomeABSTRACT
The onset of diabetic retinopathy correlates with the long-term quality of glycemic control. A 17-yr-old adolescent with type 1 diabetes presented unexpectedly with acute non-proliferative retinopathy despite good glycemic control. Two months later chronic myeloid leukemia (CML) was diagnosed. Chemotherapy was initiated and within a few weeks the patient was in full remission concerning leukemia. Retinopathy completely resolved within 8 months. The patient was in good metabolic control throughout the course. To our knowledge, this is the first report of CML-triggered retinopathy in a well-controlled diabetic adolescent. In case of unexpected retinopathy in patients with type 1 diabetes, other potential causes of retinopathy should be considered.
Subject(s)
Diabetes Mellitus, Type 1/complications , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/physiopathology , Paraneoplastic Syndromes, Ocular/etiology , Adolescent , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Diagnostic Errors , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Male , Paraneoplastic Syndromes, Ocular/diagnosis , Paraneoplastic Syndromes, Ocular/prevention & control , Remission Induction , Severity of Illness IndexABSTRACT
Inflammatory cytokines and growth factors drive angiogenesis independently; however, their integrated role in pathologic and physiologic angiogenesis is not fully understood. Suppressor of cytokine signaling-3 (SOCS3) is an inducible negative feedback regulator of inflammation and growth factor signaling. In the present study, we show that SOCS3 curbs pathologic angiogenesis. Using a Cre/Lox system, we deleted SOCS3 in vessels and studied developmental and pathologic angiogenesis in murine models of oxygen-induced retinopathy and cancer. Conditional loss of SOCS3 leads to increased pathologic neovascularization, resulting in pronounced retinopathy and increased tumor size. In contrast, physiologic vascularization is not regulated by SOCS3. In vitro, SOCS3 knockdown increases proliferation and sprouting of endothelial cells costimulated with IGF-1 and TNFα via reduced feedback inhibition of the STAT3 and mTOR pathways. These results identify SOCS3 as a pivotal endogenous feedback inhibitor of pathologic angiogenesis and a potential therapeutic target acting at the converging crossroads of growth factor- and cytokine-induced vessel growth.