2026
Invest Ophthalmol Vis Sci 2026 Jul 1;67(8):1. doi: 10.1167/iovs.67.8.1.
Degeneration of Interpericyte Tunneling Nanotubes Can Occur in the Absence of Pericyte Loss in Diabetic Retina Disease
Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Western Australia. Lions Eye Institute, The University of Western Australia, Perth, Western Australia.
Service type: Stock strains
Abstract
Purpose: Interpericyte tunneling nanotubes (IP-TNTs) synchronize pericyte-pericyte communication and regulate microvascular perfusion, processes disrupted in early diabetic retina disease (DRD). We conducted a comprehensive histological examination of IP-TNTs in the normal and diabetic retina using the streptozotocin (STZ)-induced rat model. Methods: High-resolution confocal microscopy was used to assess IP-TNT density, morphology, and their interactions with pericytes and retinal glia. Quantitative analysis was performed on vessel density, capillary diameter, pericyte distribution, and IP-TNT characteristics across three retinal vascular layers: superior vascular plexus (SVP), intermediate capillary plexus, and deep capillary plexus (DCP). Results: IP-TNTs were present across all retinal vascular plexuses, with the highest density in the SVP and DCP. Diabetic retinas exhibited a significant reduction in IP-TNT density, length, and morphological diversity, particularly in the DCP. The loss of IP-TNTs occurred independently of capillary loss and was associated with preserved vessel density and increased pericyte numbers. Notably, there was a shift in IP-TNT phenotype, with a significant increase in Type 1 (soma-to-soma) IP-TNTs in the DCP of diabetic rats. IP-TNTs were closely associated with retinal glial cells, including astrocytes and Müller cells, suggesting a role in neurovascular-glial interactions. Conclusion: Our findings indicate that IP-TNTs are critical components of the retinal microvascular network, and their early degeneration in diabetes may contribute to impaired microvascular autoregulation and pericyte dysfunction. The selective loss of IP-TNTs in the DCP highlights their potential as early biomarkers of diabetic microvascular injury. Modulating IP-TNT stability may represent a promising strategy for early intervention in diabetic retinopathy.
View Publication
