PPAR-gamma, Microglial Cells, and Ocular Inflammation: New Venues for Potential Therapeutic Approaches
Fiorella Malchiodi-Albedi1, Andrea Matteucci, Antonietta Bernardo
1Departmento di Ambiente e Connessa Prevenzione Primaria, Istituto Superiore di Sanità, 00161 Rome, Italy.
Abstract:
The last decade has witnessed an increasing interest for the role played by the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in controlling inflammation in peripheral organs as well as in the brain. Activation of PPAR-gamma has been shown to control the response of microglial cells, the main macrophage population found in brain parenchyma, and limit the inflammation. The anti-inflammatory capacity of PPAR-gamma agonists has led to the hypothesis that PPAR-gamma might be targeted to modulate degenerative brain diseases in which inflammation has been increasingly recognized as a significant component. Recent experimental evidence suggests that PPAR-gamma agonists could be exploited to treat ocular diseases such as diabetic retinopathy, age-related macular degeneration, autoimmune uveitis, and optic neuritis where inflammation has relevant role. Additional PPAR-gamma agonist beneficial effects could involve amelioration of retinal microcirculation and inhibition of neovascularization. However, PPAR-gamma activation could, in some instances, aggravate the ocular pathology, for example, by increasing the synthesis of vascular endothelial growth factor, a proangiogenic factor that could trigger a vicious circle and further deteriorate retinal perfusion. The development of new in vivo and in vitro models to study ocular inflammation and how to modulate for the eye benefit will be instrumental for the search of effective therapies.
Insights
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists show potential for treating inflammatory brain and eye diseases. However, careful consideration of their dual effects on ocular inflammation is crucial for therapeutic development.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays a key role in regulating inflammation in both the brain and peripheral organs.
- PPAR-gamma activation influences microglial cell responses, crucial for managing neuroinflammation.
Purpose of the Study:
- To explore the therapeutic potential of PPAR-gamma agonists in neurodegenerative and ocular inflammatory diseases.
- To evaluate the dual role of PPAR-gamma activation in ocular pathologies, including potential benefits and risks.
Main Methods:
- Review of experimental evidence on PPAR-gamma agonists in inflammatory conditions.
- Analysis of PPAR-gamma's impact on microglial cells and ocular disease models.
Main Results:
- PPAR-gamma agonists demonstrate anti-inflammatory effects relevant to conditions like diabetic retinopathy, age-related macular degeneration, uveitis, and optic neuritis.
- Potential benefits include improved retinal microcirculation and reduced neovascularization.
- Conversely, PPAR-gamma activation may exacerbate ocular pathology by increasing vascular endothelial growth factor (VEGF).
Conclusions:
- PPAR-gamma agonists represent a promising therapeutic target for inflammatory brain and ocular diseases.
- Further research using advanced in vivo and in vitro models is essential to optimize PPAR-gamma modulation for ocular benefit and mitigate adverse effects.
