The RNA‐binding protein and stress granule component ATAXIN‐2 is expressed in mouse and human tissues associated with glaucoma pathogenesis

• Published in: Journal of comparative neurology (1911) Vol. 530; no. 2; pp. 537 - 552
• Main Authors: Sundberg, Chad A., Lakk, Monika, Paul, Sharan, Figueroa, Karla, Scoles, Daniel R., Pulst, Stefan M., Križaj, David
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.02.2022; Wiley Subscription Services, Inc
• Subjects: Amacrine cells; Amacrine Cells - metabolism; Animals; Ataxin; Ataxin-2 - metabolism; ATXN2; Autophagy; Bipolar cells; Degeneration; Dendrites; Dendrites - metabolism; Disease Models, Animal; Glaucoma; Glaucoma, Open-Angle - physiopathology; Humans; Immunofluorescence; Localization; Mice; Motor neurons; Phagocytosis; Polyglutamine; Polymorphism, Single Nucleotide; primary open angle glaucoma; Purkinje cells; Retina; Retina - physiology; Retinal ganglion cells; Retinal Ganglion Cells - metabolism; RNA-binding protein; SCA2; Single-nucleotide polymorphism; Spinocerebellar ataxia; stress granules; Stress Granules - pathology; Trinucleotide repeat diseases; γ-Aminobutyric acid; ATXN2; RNA-binding protein; autophagy; primary open angle glaucoma; SCA2; stress granules; retinal ganglion cells
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.25228

Polyglutamine repeat expansions in the Ataxin‐2 (ATXN2) gene were first implicated in Spinocerebellar Ataxia Type 2, a disease associated with degeneration of motor neurons and Purkinje cells. Recent studies linked single nucleotide polymorphisms in the gene to elevated intraocular pressure in primary open angle glaucoma (POAG); yet, the localization of ATXN2 across glaucoma‐relevant tissues of the vertebrate eye has not been thoroughly examined. This study characterizes ATXN2 expression in the mouse and human retina, and anterior eye, using an antibody validated in ATXN2−/− retinas. ATXN2‐ir was localized to cytosolic sub compartments in retinal ganglion cell (RGC) somata and proximal dendrites in addition to GABAergic, glycinergic, and cholinergic amacrine cells in the inner plexiform layer (IPL) and displaced amacrine cells. Human, but not mouse retinas showed modest immunolabeling of bipolar cells. ATXN2 immunofluorescence was prominent in the trabecular meshwork and pigmented and nonpigmented cells of the ciliary body, with analyses of primary human trabecular meshwork cells confirming the finding. The expression of ATXN2 in key POAG‐relevant ocular tissues supports the potential role in autophagy and stress granule formation in response to ocular hypertension. The RNA‐binding protein Ataxin 2 (ATXN2) is associated with neurodegenerative diseases and vision loss. Retinal ATXN2 is confined to spiking neurons (ganglion cells and amacrine cells) and largely absent from photoreceptors/bipolar cells and glia. Prominent expression in the trabecular meshwork and the ciliary body suggests relevance to glaucoma.