Departmental Affiliation and City, State, Zip for All Authors

North Texas Eye Research Institute, UNT Health Science Center, Fort Worth, TX, 76107

Scientific Abstract

Glaucoma is the second leading cause of blindness worldwide. Acid-sensing ion channels (ASICs) increased in animal models of glaucoma but the exact mechanism is still unknown. Several cytokines and hormones such as steroids (DEX), endothelin-1 (ET-1), tumor-necrosis factor-alpha (TNFα) and transforming growth factor-beta-2 (TGFβ2) are elevated in glaucoma or even induce glaucoma. The purpose of these experiments is to evaluate the effects of DEX, ET-1, TNFα, and TGFβ2 on ASICs' gene expression. Both human primary brain and retinal astrocytes were treated for 24hr with DEX (100 nM), ET-1 (250 nM), TNFα (10ng/ml), or TGFβ2 (10ng/ml) followed by RNA isolation, cDNA synthesis and real-time PCR to quantify changes in ASIC1, ASIC2, and ASIC3 gene expression. Only TNFα consistently induced down regulation of ASIC1. Such a finding is very important as it may suggest that TNFα-induced down regulation of ASIC1 impairs proton-buffering in astrocytes and neurons that may lead to neuronal cell death under ischemic conditions. Funded by the Department of Health and Human Services, National Institute of Health, National Heart, Lung and Blood Institute, SMART Grant 5R25HL007786-25 to Dr. Jamboor K. Vishwanatha, Ph.D.

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AGENTS MODULATING ACID-SENSING ION CHANNELS (ASICS) IN HUMAN PRIMARY BRAIN AND RETINAL ASTROCYTES

Glaucoma is the second leading cause of blindness worldwide. Acid-sensing ion channels (ASICs) increased in animal models of glaucoma but the exact mechanism is still unknown. Several cytokines and hormones such as steroids (DEX), endothelin-1 (ET-1), tumor-necrosis factor-alpha (TNFα) and transforming growth factor-beta-2 (TGFβ2) are elevated in glaucoma or even induce glaucoma. The purpose of these experiments is to evaluate the effects of DEX, ET-1, TNFα, and TGFβ2 on ASICs' gene expression. Both human primary brain and retinal astrocytes were treated for 24hr with DEX (100 nM), ET-1 (250 nM), TNFα (10ng/ml), or TGFβ2 (10ng/ml) followed by RNA isolation, cDNA synthesis and real-time PCR to quantify changes in ASIC1, ASIC2, and ASIC3 gene expression. Only TNFα consistently induced down regulation of ASIC1. Such a finding is very important as it may suggest that TNFα-induced down regulation of ASIC1 impairs proton-buffering in astrocytes and neurons that may lead to neuronal cell death under ischemic conditions. Funded by the Department of Health and Human Services, National Institute of Health, National Heart, Lung and Blood Institute, SMART Grant 5R25HL007786-25 to Dr. Jamboor K. Vishwanatha, Ph.D.

Manuscript Number

1006