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Experimental Models for Study of Retinal Pigment Epithelial Physiology and Pathophysiology
Published on: November 6, 2010
IGFBP-3 and TNF-α regulate retinal endothelial cell apoptosis
Qiuhua Zhang1, Youde Jiang, Matthew J Miller
1Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Investigative Ophthalmology & Visual Science
|July 23, 2013
Summary
Loss of insulin-like growth factor binding protein 3 (IGFBP-3) signaling causes retinal neuronal changes and apoptosis, mimicking early diabetic retinopathy. This involves increased TNF-α, suggesting a potential therapeutic target for retinal diseases.
Area of Science:
- Ophthalmology
- Endocrinology
- Cell Biology
Background:
- Diabetic retinopathy (DR) involves complex retinal changes.
- Insulin-like growth factor binding protein 3 (IGFBP-3) plays a role in cellular regulation.
- Tumor necrosis factor-alpha (TNF-α) is implicated in inflammatory processes within the retina.
Purpose of the Study:
- To investigate the role of IGFBP-3 signaling in the retina.
- To determine if loss of IGFBP-3 leads to retinal neuronal changes similar to early diabetes.
- To explore the interaction between IGFBP-3 and TNF-α in retinal endothelial cells.
Main Methods:
- Evaluation of neuronal, vascular, and functional changes in IGFBP-3 knockout (KO) mice compared to wild-type littermates.
- Culture of retinal endothelial cells (REC) under normoglycemic and hyperglycemic conditions.
- Treatment of REC with TNF-α and Compound 49b (a β-adrenergic receptor agonist) to assess protein interactions.
Main Results:
- IGFBP-3 KO mice exhibited reduced electroretinogram amplitudes (B-wave, oscillatory potentials) and increased apoptosis.
- Significant reductions in retinal thickness and ganglion cell layer numbers were observed in IGFBP-3 KO mice.
- IGFBP-3 inhibited apoptosis in REC, while TNF-α promoted it, indicating an antagonistic relationship.
Conclusions:
- Loss of IGFBP-3 signaling induces a phenotype resembling early diabetic retinopathy neuronal changes.
- Increased TNF-α levels are associated with IGFBP-3 deficiency in the retina.
- The balance between IGFBP-3 and TNF-α activity may dictate retinal endothelial cell apoptosis.
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