Modelling neurodegeneration and inflammation in early diabetic retinopathy using 3D human retinal organoids

使用 3D 人类视网膜类器官模拟早期糖尿病视网膜病变中的神经退行性变和炎症

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作者:Luisa de Lemos, Pedro Antas, Inês S Ferreira, Inês Paz Santos, Beatriz Felgueiras, Catarina M Gomes, Catarina Brito, Miguel C Seabra, Sandra Tenreiro

Conclusion

The data provided highlight the utility of retinal organoid technology in modelling early-stage DR. This offers new avenues for the development of targeted therapeutic interventions on neurodegeneration and inflammation in the initial phase of DR, potentially slowing the disease's progression.

Methods

Here, we used human-induced pluripotent stem cells (hiPSCs) differentiated into three-dimensional (3D) retinal organoids, which resemble the complexity of the retinal tissue. Retinal organoids were subjected to high-glucose conditions to generate a model of early DR.

Purpose

Diabetic retinopathy (DR) is a complication of diabetes and a primary cause of visual impairment amongst working-age individuals. DR is a degenerative condition in which hyperglycaemia

Results

Our model showed well-established molecular and cellular features of early DR, such as (i) loss of retinal ganglion and amacrine cells; (ii) glial reactivity and inflammation, with increased expression of the vascular endothelial-derived growth factor (VEGF) and interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) secretion; and (iii) increased levels of reactive oxygen species accompanied by activation of key enzymes involved in antioxidative stress response.

Supplementary Information

The online version contains supplementary material available at 10.1007/s44164-024-00068-1.

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