Dataset Information

Ocular phenotypes in a mouse model of impaired glucocerebrosidase activity.

ABSTRACT: Mutations in the GBA1 gene encoding glucocerebrosidase (GCase) are linked to Gaucher (GD) and Parkinson's Disease (PD). Since some GD and PD patients develop ocular phenotypes, we determined whether ocular phenotypes might result from impaired GCase activity and the corresponding accumulation of glucosylceramide (GluCer) and glucosylsphingosine (GluSph) in the Gba1^D409V/D409V knock-in (Gba KI/KI; "KI") mouse. Gba KI mice developed age-dependent pupil dilation deficits to an anti-muscarinic agent; histologically, the iris covered the anterior part of the lens with adhesions between the iris and the anterior surface of the lens (posterior synechia). This may prevent pupil dilation in general, beyond an un-responsiveness of the iris to anti-muscarinics. Gba KI mice displayed atrophy and pigment dispersion of the iris, and occlusion of the iridocorneal angle by pigment-laden cells, reminiscent of secondary open angle glaucoma. Gba KI mice showed progressive thinning of the retina consistent with retinal degeneration. GluSph levels were increased in the anterior and posterior segments of the eye, suggesting that accumulation of lipids in the eye may contribute to degeneration in this compartment. We conclude that the Gba KI model provides robust and reproducible eye phenotypes which may be used to test for efficacy and establish biomarkers for GBA1-related therapies.

SUBMITTER: Weber M

PROVIDER: S-EPMC7971029 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Ocular phenotypes in a mouse model of impaired glucocerebrosidase activity.

Weber Martin M Min Sang-Won SW Truong Tom T Hung Jeffrey J Dale Stephanie S Reichelt Mike M Ubhayakar Savita S Cain-Hom Carol C Baca Miriam M Jiang Zhiyu Z Li Qingling Q Brendza Robert R Lin Han H Kung Chung C Forrest William F WF Quiason-Huynh Cristine C Sandoval Wendy W Chen Buyun B Deng Yuzhong Y Easton Amy A Foreman Oded O Sene Abdoulaye A Bingol Baris B

Scientific reports 20210316 1

Mutations in the GBA1 gene encoding glucocerebrosidase (GCase) are linked to Gaucher (GD) and Parkinson's Disease (PD). Since some GD and PD patients develop ocular phenotypes, we determined whether ocular phenotypes might result from impaired GCase activity and the corresponding accumulation of glucosylceramide (GluCer) and glucosylsphingosine (GluSph) in the Gba1<sup>D409V/D409V</sup> knock-in (Gba KI/KI; "KI") mouse. Gba KI mice developed age-dependent pupil dilation deficits to an anti-musca ...[more]

PMID: 33727605

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Dataset Information

Ocular phenotypes in a mouse model of impaired glucocerebrosidase activity.

Publications

Ocular phenotypes in a mouse model of impaired glucocerebrosidase activity.

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