Ma, J.-X. | bioRxiv Science

bioRxiv2025

Intranasal Insulin Mediates Neurodegeneration in Diabetic Retinopathy via Regulation of Inflammatory and Apoptotic Pathways

Neurodegenerative changes predominate in early stages of diabetic retinopathy but effective therapies are lacking. Insulin treatment decreases neurodegeneration and intranasal insulin has been shown to reach the central nervous system in neurodegenerative diseases like dementia. We tested the hypothesis that intranasal insulin can decrease retinal neurodegeneration using the C57BL/KsJ-db/db transgenic diabetic (db/db) mouse model. Compared to the non-diabetic wildtype mice given intranasal saline, we observed decreased electroretinogram b-wave and oscillatory potential amplitudes in db/db mice treated with intranasal saline but not in the db/db mice treated with 2 units of intranasal insulin daily over 10 weeks. When compared to the non-diabetic intranasal saline control, we also observed decreased outer retinal thickness in the db/db mice given intranasal saline but this effect was attenuated in the db/db mice treated with intranasal insulin. GFAP immunoreactivity and caspase cell count were similarly elevated in the db/db mice treated with intranasal saline but not intranasal insulin. Mean blood glucose measurements increased 30 minutes after both intranasal saline and insulin treatment. Transcriptomic analysis revealed downregulation of inflammatory and apoptotic genes in the retina of db/db mice treated with intranasal insulin when compared to saline. In summary, treatment with intranasal insulin prevents the depression of b-waves and oscillatory potentials, decreases the attenuation of outer retinal thickness, reduces caspase cell count and GFAP immunostaining, and downregulates the transcription of inflammatory and apoptotic genes in the retina of db/db mice without exerting peripheral glucose lowering effects. Taken together, our results suggest that intranasal insulin can reduce neurodegeneration in diabetic retinopathy by improving retinal neuronal function, decreasing reactive gliosis and cell death, and modulating the expression of inflammatory and apoptotic genes.

biochemistry↗

bioRxiv2021

Computationally reconstructed interactome of Bradyrhizobium diazoefficiens USDA110 reveals novel functional modules and protein hubs for symbiotic nitrogen fixation

Symbiotic nitrogen fixation is an important part of the nitrogen biogeochemical cycles and the main nitrogen source of the biosphere. As a classical model system for symbiotic nitrogen fixation, rhizobium-legume systems have been studied elaborately for decades. Detailed panorama about the molecular mechanism of the communication and coordination between rhizobia and host plants is becoming clearer. For more systematic insights, there is an increasing demand on new studies integrating multi-omics information. Here we present a comprehensive computational framework, integrating the reconstructed protein interactome of B. diazoefficiens USDA110 with its transcriptome and proteome data, to study the complex protein-protein interaction (PPI) network involved in the symbiosis system. We reconstructed the interactome of B. diazoefficiens USDA110 by computational approaches. Based on the comparison of interactomes between B. diazoefficiens USDA110 and other rhizobia, we inferred that the slow growth of B. diazoefficiens USDA110 may owe to the requirement of more protein modifications and further identified 36 conserved functional PPI modules. Integrated with transcriptome and proteome data, interactomes representing free-living cell and symbiotic nitrogen-fixing (SNF) bacteroid were obtained. Based on the SNF interactome, a core-sub-PPI-network for symbiotic nitrogen fixation was determined and 9 novel functional modules and 11 key protein hubs playing key roles for symbiosis were identified. The reconstructed interactome of B. diazoefficiens USDA110 may serve as a valuable reference for studying the mechanism underlying the SNF system of rhizobia and legumes.

systems biology↗