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The pancreas is a mixed gland primarily composed of exocrine tissue, which secretes digestive enzymes into the digestive tract, and an endocrine component organized into small clusters known as islets of Langerhans, constituting approximately 1% of the pancreatic mass. Each adult islet contains an average of 1,500 cells, including beta-, alpha- and delta-cells, which produce and secrete insulin (INS), glucagon (GCG), and somatostatin (SST) respectively. The destruction of insulin-producing beta-cells or the defective insulin secretion give rise to type 1 and type 2 diabetes mellitus, respectively. These chronic metabolic disorders are characterized by the dysregulation of glucose homeostasis. 

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Current Issue

Metabolic plasticity in a Pde6bSTOP/STOP retinitis pigmentosa mouse model following rescue

Monika Ayten, Nundehui Díaz-Lezama, Hanaa Ghanawi, Felia C. Haffelder, ... Susanne F. Koch

Metabolic plasticity in a Pde6bSTOP/STOP retinitis pigmentosa mouse model following rescue

Objective

Retinitis pigmentosa (RP) is a hereditary retinal disease characterized by progressive photoreceptor degeneration, leading to vision loss. The best hope for a cure for RP lies in gene therapy. However, given that RP patients are most often diagnosed in the midst of ongoing photoreceptor degeneration, it is unknown how the retinal proteome changes as RP disease progresses, and which changes can be prevented, halted, or reversed by gene therapy.

Methods

Here, we used a Pde6b-deficient RP gene therapy mouse model and performed untargeted proteomic analysis to identify changes in protein expression during degeneration and after treatment.

Results

We demonstrated that Pde6b gene restoration led to a novel form of homeostatic plasticity in rod phototransduction which functionally compensates for the decreased number of rods. By profiling protein levels of metabolic genes and measuring metabolites, we observed an upregulation of proteins associated with oxidative phosphorylation in mutant and treated photoreceptors.

Conclusion

In conclusion, the metabolic demands of the retina differ in our Pde6b-deficient RP mouse model and are not rescued by gene therapy treatment. These findings provide novel insights into features of both RP disease progression and long-term rescue with gene therapy.

Articles in Press

Metabolic plasticity in a Pde6bSTOP/STOP retinitis pigmentosa mouse model following rescue

Monika Ayten, Nundehui Díaz-Lezama, Hanaa Ghanawi, Felia C. Haffelder, ... Susanne F. Koch

Metabolic plasticity in a Pde6bSTOP/STOP retinitis pigmentosa mouse model following rescue

Objective

Retinitis pigmentosa (RP) is a hereditary retinal disease characterized by progressive photoreceptor degeneration, leading to vision loss. The best hope for a cure for RP lies in gene therapy. However, given that RP patients are most often diagnosed in the midst of ongoing photoreceptor degeneration, it is unknown how the retinal proteome changes as RP disease progresses, and which changes can be prevented, halted, or reversed by gene therapy.

Methods

Here, we used a Pde6b-deficient RP gene therapy mouse model and performed untargeted proteomic analysis to identify changes in protein expression during degeneration and after treatment.

Results

We demonstrated that Pde6b gene restoration led to a novel form of homeostatic plasticity in rod phototransduction which functionally compensates for the decreased number of rods. By profiling protein levels of metabolic genes and measuring metabolites, we observed an upregulation of proteins associated with oxidative phosphorylation in mutant and treated photoreceptors.

Conclusion

In conclusion, the metabolic demands of the retina differ in our Pde6b-deficient RP mouse model and are not rescued by gene therapy treatment. These findings provide novel insights into features of both RP disease progression and long-term rescue with gene therapy.

2022 impact factor: 6.6

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