Multiomic analysis of human diabetic retinal disease reveals severity and region-specific impairment of the retinal neurovascular unit
Abstract
Diabetic retinal disease (DRD) is the leading cause of preventable blindness worldwide, but current therapeutic options only target vascular components in late-stage vision-threatening disease because the molecular mechanisms underlying early disease and affecting the whole retina are poorly understood. This study aimed to uncover disease-driving events of DRD using a multiomic approach to compare peripheral and central retinal tissue from human donors with diabetes without retinopathy or varying severity of diabetic retinal disease to their demographically matched non-diabetic counterparts. Integrative proteo-transcriptomic analysis combined with targeted validation reveals stage and region-specific disease drivers affecting the whole neurovascular unit defined by dysfunction in neuronal signaling, retinal metabolism, and neuroinflammation through activation of complement signaling. Further, our study reveals evidence of correlation of a subset of these retinal changes in the vitreous space in early disease, pointing to the specific role of this ocular fluid for DRD diagnosis and management. These findings are critical for the development of targeted therapeutic approaches to treat or prevent progression of DRD to vision threatening disease.
Related
- Diabetic retinal neurovascular unit injury: mechanisms, imaging evaluation, and integrated therapeutic strategies
- Extracellular vesicles in vascular cognitive impairment and dementia: a neurovascular evidence map for patient stratification and clinical translation
- Animal models for investigating post-stroke cognitive impairment: A neurovascular trafficking perspective.
- Downregulation of Trpv4 and Klf2 in brain microvessels is associated with the progression of neurovascular dysfunction and cognitive impairment in a model of heart failure with preserved ejection fraction
- Modified Dioscorea pills ameliorate cognitive impairment induced by chronic cerebral hypoperfusion via restoring the hippocampal neurovascular unit
BibTeX
@misc{fort2026multiomic,
title = {{Multiomic analysis of human diabetic retinal disease reveals severity and region-specific impairment of the retinal neurovascular unit}},
author = {Patrice Fort and Rachana Haliyur and Yang Shan and Nicholas J Carruthers and Lynda Elghazi and Christopher Gates and Venkatesha Basrur and Felipe de Veiga Leprevost and Alexey Nesvizhskii},
howpublished = {Research Square},
year = {2026},
month = oct,
doi = {10.21203/rs.3.rs-11394372/v1},
url = {https://doi.org/10.21203/rs.3.rs-11394372/v1},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Multiomic analysis of human diabetic retinal disease reveals severity and region-specific impairment of the retinal neurovascular unit
AU - Patrice Fort
AU - Rachana Haliyur
AU - Yang Shan
AU - Nicholas J Carruthers
AU - Lynda Elghazi
AU - Christopher Gates
AU - Venkatesha Basrur
AU - Felipe de Veiga Leprevost
AU - Alexey Nesvizhskii
PY - 2026
DA - 2026/10/30
PB - Research Square
DO - 10.21203/rs.3.rs-11394372/v1
UR - https://doi.org/10.21203/rs.3.rs-11394372/v1
AB - Diabetic retinal disease (DRD) is the leading cause of preventable blindness worldwide, but current therapeutic options only target vascular components in late-stage vision-threatening disease because the molecular mechanisms underlying early disease and affecting the whole retina are poorly understood. This study aimed to uncover disease-driving events of DRD using a multiomic approach to compare peripheral and central retinal tissue from human donors with diabetes without retinopathy or varying severity of diabetic retinal disease to their demographically matched non-diabetic counterparts. Integrative proteo-transcriptomic analysis combined with targeted validation reveals stage and region-specific disease drivers affecting the whole neurovascular unit defined by dysfunction in neuronal signaling, retinal metabolism, and neuroinflammation through activation of complement signaling. Further, our study reveals evidence of correlation of a subset of these retinal changes in the vitreous space in early disease, pointing to the specific role of this ocular fluid for DRD diagnosis and management. These findings are critical for the development of targeted therapeutic approaches to treat or prevent progression of DRD to vision threatening disease.
SN - 2693-5015
ER -