Modulation of diabetes-related retinal pathophysiology by PTX3
Varun Pathak1, Pietro M Bertelli1, Edoardo Pedrini1
1The Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, United Kingdom.
Summary
Pentraxin 3 (PTX3) exacerbates diabetic retinopathy (DR) by enhancing inflammation and neurodegeneration. Eliminating PTX3 in mice protected against DR pathology and preserved vision, highlighting PTX3 as a therapeutic target for diabetes complications.
Area of Science:
- Ophthalmology
- Immunology
- Endocrinology
Background:
- Diabetic retinopathy (DR) is a diabetes complication involving vascular damage and neuroinflammation.
- Pentraxin 3 (PTX3) is an inflammatory mediator, but its role in DR is unknown.
Purpose of the Study:
- To investigate the role of PTX3 in the pathogenesis of diabetic retinopathy.
Main Methods:
- Assessed PTX3 levels in diabetic mouse retinas and human DR datasets.
- Utilized PTX3 knockout (PTX3KO) mice in a diabetes model.
- Evaluated DR hallmarks, visual function, and inflammatory responses in PTX3KO mice.
Main Results:
- PTX3 levels were elevated in diabetic retinas.
- Diabetic PTX3KO mice showed reduced gliosis, microglia activation, and vasodegeneration.
- PTX3KO mice exhibited preserved visual function and reduced neuroinflammation.
- PTX3 promoted an inflammatory phenotype in retinal macroglia and was essential for TNF-α-induced gliosis.
Conclusions:
- PTX3 enhances sterile inflammation in diabetic retinopathy.
- PTX3 contributes to DR pathogenesis and visual impairment.
- PTX3 represents a potential therapeutic target for managing diabetic retinopathy.
