Objective:To assess endothelin B receptor(ETbR)expression in human glaucomatous optic nerves and the spatial relationship between ETbR and astrocytes.Methods:Twenty-six eyes from 16 glaucoma patients and 10 normal control subjects were immunohistochemically labeled with antibodies to ETbR.The immunoreactivity was quantified and compared between normal and glaucomatous eyes with an image analysis system.Tissues were also double-labeled for ETbR and astrocytes.In addition,the optic nerve of a monkey with regional degeneration induced by laser coagulation was examined with the same techniques.Results:The frequency of positive ETbR immunoreactivity was higher in human glaucomatous optic nerves as comparedwith age-matched controls(9/16 vs 1/10,P=.02).The ETbR immunoreactivity colocalized with astrocytic processes andwas quantitatively higher in the glaucomatous eyes(P=.02).In the monkey,the regions of degeneration showed increased ETbR associated with reactive astrocytes and was highest at the borders between normal areas and degeneration.Conclusion:Increased ETbR immunoreactivity in diseased optic nerves and its association with astrocytes suggest that the glia-endothelin system may be involved in the pathologic mechanisms of neuronal degeneration.Clinical Relevance:The study supports the clinical observation of endothelin involvement in glaucoma and provides direct evidence that the endothelin system is associated with glaucomatous pathologic abnormalities. Objective: To assess endothelin B receptor (ETbR) expression in human glaucomatous optic nerves and the spatial relationship between ETbR and astrocytes. Methods: Twenty-six eyes from 16 glaucoma patients and 10 normal control subjects were immunohistochemically labeled with antibodies to ETbR. was quantified and compared between normal and glaucomatous eyes with an image analysis system. Tissues were also double-labeled for ETbR and astrocytes. In addition, the optic nerve of a monkey with regional degeneration induced by laser coagulation was examined with the same techniques. Results : The frequency of positive ETbR immunoreactivity was higher in human glaucomatous optic nerves as compared with age-matched controls (9/16 vs 1/10, P = .02). The ETbR immunoreactivity colocalized with astrocytic processes and was quantitatively higher in the glaucomatous eyes ( P = .02). In the monkey, the regions of degeneration showed increased ETbR associated with reactive astrocytes and was highest at the borders between normal areas and degeneration. Confound: Increased ETbR immunoreactivity in diseased optic nerves and its association with astrocytes suggest that the glia-endothelin system may be involved in the pathologic mechanisms of neuronal degeneration. Clinical Relevance: The study supports the clinical observation of endothelin involvement in glaucoma and provides direct evidence that the endothelin system is associated with glaucomatous pathologic abnormalities.