Presentation Title (IN ALL CAPS)

REGULATION OF CYTOCHROME C OXIDASE COPPER CHAPERONE, ATP SYNTHASE H+ TRANSPORTING MITOCHONDRIAL F0 COMPLEX SUBUNIT D, AND FORKHEAD BOX PROTEIN O1 GENES IN A RAT MODEL OF GLAUCOMA

Departmental Affiliation and City, State, Zip for All Authors

St. Mary's University, San Antonio, TX, 78228; North Texas Eye Research Institute, Fort Worth, TX 76107; North Texas Eye Research Institute, Fort Worth, TX 76107; North Texas Eye Research Institute, Fort Worth, TX 76107

Scientific Abstract

Glaucoma, a leading cause of blindness, is an optic neuropathy characterized by an increase in intraocular pressure (IOP), degeneration of the optic nerve head and apoptosis of retinal ganglion cells (RGCs) resulting in vision loss. It is commonly associated with elevated IOP, but even after lowering IOP with medications, laser treatment, or surgery (Vass et al., 2007), disease progression continues, therefore neuroprotection of optic nerve axons and RGCs becomes important as an additional therapeutic modality. Endothelin-1 (ET-1) is a 21-amino acid peptide whose levels are elevated in aqueous humor and plasma of glaucoma patients (Tezel et al., 1997; Choritz et al., 2012; Lopez-Riquelme et al., 2015). ET-1 acts by primarily binding to G-protein-coupled receptors namely, endothelin A (ETA) and endothelin B (ETB) causing neuronal damage in glaucoma (Yorio et al., 2002; Krishnamoorthy et al., 2008). In the current study, rats were intravitreally injected with ET-1, euthanized 24 hours post-injection and retinal sections were obtained. Immunohistochemical analysis was conducted following immunostaining with specific antibodies to assess expression of mitochondrial genes cytochrome c oxidase copper chaperone (Cox17), an enzyme of the mitochondrial respiratory chain, ATP synthase H+ transporting mitochondrial F0 complex subunit D (ATP5H), an enzyme catalyzing mitochondrial ATP synthesis, and forkhead box protein O1 (FoxO1), a gene associated with neurodegeneration. These genes were previously found to be differentially expressed by RNA-seq in RGCs following ET-1 treatment. Overall, ET-1 treatment altered expression of several genes affecting mitochondrial bioenergetics and metabolism which can further contribute to mechanisms underlying ET-1’s neurodegenerative effects in glaucoma.

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REGULATION OF CYTOCHROME C OXIDASE COPPER CHAPERONE, ATP SYNTHASE H+ TRANSPORTING MITOCHONDRIAL F0 COMPLEX SUBUNIT D, AND FORKHEAD BOX PROTEIN O1 GENES IN A RAT MODEL OF GLAUCOMA

Glaucoma, a leading cause of blindness, is an optic neuropathy characterized by an increase in intraocular pressure (IOP), degeneration of the optic nerve head and apoptosis of retinal ganglion cells (RGCs) resulting in vision loss. It is commonly associated with elevated IOP, but even after lowering IOP with medications, laser treatment, or surgery (Vass et al., 2007), disease progression continues, therefore neuroprotection of optic nerve axons and RGCs becomes important as an additional therapeutic modality. Endothelin-1 (ET-1) is a 21-amino acid peptide whose levels are elevated in aqueous humor and plasma of glaucoma patients (Tezel et al., 1997; Choritz et al., 2012; Lopez-Riquelme et al., 2015). ET-1 acts by primarily binding to G-protein-coupled receptors namely, endothelin A (ETA) and endothelin B (ETB) causing neuronal damage in glaucoma (Yorio et al., 2002; Krishnamoorthy et al., 2008). In the current study, rats were intravitreally injected with ET-1, euthanized 24 hours post-injection and retinal sections were obtained. Immunohistochemical analysis was conducted following immunostaining with specific antibodies to assess expression of mitochondrial genes cytochrome c oxidase copper chaperone (Cox17), an enzyme of the mitochondrial respiratory chain, ATP synthase H+ transporting mitochondrial F0 complex subunit D (ATP5H), an enzyme catalyzing mitochondrial ATP synthesis, and forkhead box protein O1 (FoxO1), a gene associated with neurodegeneration. These genes were previously found to be differentially expressed by RNA-seq in RGCs following ET-1 treatment. Overall, ET-1 treatment altered expression of several genes affecting mitochondrial bioenergetics and metabolism which can further contribute to mechanisms underlying ET-1’s neurodegenerative effects in glaucoma.

Manuscript Number

1055