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Retinal response to systemic inflammation differs between sexes and neurons
Kristy T Rodríguez-Ramírez1, María Norte-Muñoz1, Fernando Lucas-Ruiz1
1Grupo de Investigación Oftalmología Experimental, Departamento de Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica, Facultad de Medicina, Universidad de Murcia, Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain.
Frontiers in Immunology
|February 22, 2024
Summary
Systemic inflammation from lipopolysaccharide (LPS) causes sex-specific retinal damage in mice. Targeting NLRP3 inflammasome and apoptosis pathways protected the retina, especially in females.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Neurological dysfunction and glial activation are hallmarks of severe infections like sepsis.
- Sexual dimorphism exists in systemic inflammation responses, yet comparative studies are scarce.
- Investigating sex-specific retinal effects of systemic inflammation is crucial.
Purpose of the Study:
- To examine the impact of lipopolysaccharide (LPS)-induced systemic inflammation on the male and female mouse retina.
- To evaluate the protective potential of NLRP3 inflammasome and extrinsic apoptosis pathway antagonism against LPS-induced retinal damage.
Main Methods:
- Mice received intraperitoneal lipopolysaccharide (LPS).
- Retinal function and structure were assessed using electroretinography and optical coherence tomography.
- Retinal ganglion cell (RGC) survival, microglial activation, and cytokine levels were analyzed; treatment groups received P2X7R and TNFR1 antagonists.
Main Results:
- LPS induced transient retinal dysfunction, RGC loss, swelling, and inflammation in both sexes.
- Males exhibited greater RGC death, slower recovery, and elevated lymphotoxin alpha compared to females.
- P2X7R and TNFR1 antagonism protected RGCs and retinal function, with females showing better treatment response.
Conclusions:
- Systemic LPS causes sex-specific neuronal and retinal damage in mice.
- Targeting NLRP3 inflammasome and extrinsic apoptosis pathways offers neuroprotection in the retina.
- Preclinical studies must consider sex differences in inflammatory central nervous system diseases.
