Rod Photoreceptor-Specific Ablation of Metformin Target, AMPK, in a Preclinical Model of Autosomal Recessive Retinitis Pigmentosa

Nicholas D Nolan; Laura A Jenny; Stephen H Tsang; Xuan Cui

doi:10.1007/978-3-031-27681-1_59

Rod Photoreceptor-Specific Ablation of Metformin Target, AMPK, in a Preclinical Model of Autosomal Recessive Retinitis Pigmentosa

Adv Exp Med Biol. 2023:1415:403-408. doi: 10.1007/978-3-031-27681-1_59.

Authors

Nicholas D Nolan^{1

2

3

4}, Laura A Jenny^{2

3}, Stephen H Tsang^{1

2

3

4

5

6}, Xuan Cui^{7

8}

Affiliations

¹ Department of Biomedical Engineering, Columbia University, New York, NY, USA.
² Edward S. Harkness Eye Institute, Department of Ophthalmology, Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, NY, USA.
³ Jonas Children's Vision Care, and Bernard & Shirlee Brown Glaucoma Laboratory, Department of Ophthalmology, Columbia University, New York, NY, USA.
⁴ Columbia Stem Cell Initiative, Columbia University, New York, NY, USA.
⁵ Department of Pathology & Cell Biology, Columbia University, New York, NY, USA.
⁶ Institute of Human Nutrition, Columbia University, New York, NY, USA.
⁷ Edward S. Harkness Eye Institute, Department of Ophthalmology, Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, NY, USA. xc2342@cumc.columbia.edu.
⁸ Jonas Children's Vision Care, and Bernard & Shirlee Brown Glaucoma Laboratory, Department of Ophthalmology, Columbia University, New York, NY, USA. xc2342@cumc.columbia.edu.

PMID: 37440064
DOI: 10.1007/978-3-031-27681-1_59

Abstract

Retinal gene therapies have shown tremendous progress in the past decade, but the sheer number of disease-causing mutations makes their applicability challenging. In this study we test our hypothesis that retinitis pigmentosa-associated retinal degeneration can be prevented through AMP-activated protein kinase (AMPK)-associated metabolic pathway reprogramming using a gene-independent model of degeneration and rescue. We show that recue of photoreceptor structure and function is not achieved through our model of metabolic reprogramming. These results suggest that RP may not be treatable through AMPK pathway modulation-based therapies.

Keywords: Gene therapy; Late-stage treatment; Metabolomics; Retinal degenerations; Retinitis pigmentosa.

MeSH terms

AMP-Activated Protein Kinases / genetics
AMP-Activated Protein Kinases / metabolism
Humans
Metformin* / pharmacology
Metformin* / therapeutic use
Retina / metabolism
Retinal Rod Photoreceptor Cells / metabolism
Retinitis Pigmentosa*

Substances

AMP-Activated Protein Kinases
Metformin