Related Experiment Video
Updated: May 2, 2026
In Vivo Imaging of Cx3cr1gfp/gfp Reporter Mice with Spectral-domain Optical Coherence Tomography and Scanning Laser Ophthalmoscopy
Published on: November 11, 2017
CCL3 production by microglial cells modulates disease severity in murine models of retinal degeneration
Hideo Kohno1, Tadao Maeda, Lindsay Perusek
1Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106;
Abstract:
Many degenerative retinal diseases illustrate retinal inflammatory changes that include infiltration of microglia and macrophages into the subretinal space. In this study, we examined the role of chemokines in the Abca4(-/-)Rdh8(-/-) mouse model of Stargardt disease and the Mertk(-/-) mouse model of retinitis pigmentosa. PCR array analysis of 84 chemokines and related molecules revealed 84.6-fold elevated expression of Ccl3 (MIP-1a) 24 h after light exposure in Abca4(-/-)Rdh8(-/-) mice. Only MIP-1 chemokines, including Ccl3 and Ccl4, displayed peak expression 24 h after light exposure, and peaked earlier than the other chemokines. Secretion of Ccl3 was documented only in microglia, whereas both microglia and retinal pigment epithelium cells produced Ccl2. Exposure of Cx3Cr1(gfp/Δ)Abca4(-/-)Rdh8(-/-) mice to intense light resulted in the appearance of Cx3Cr1GFP(+) monocytes in the subretinal space. To address the in vivo role of CCL3 in retinal degeneration, Ccl3(-/-)Abca4(-/-)Rdh8(-/-) mice and Ccl3(-/-)Mertk(-/-) mice were generated. Following intense light exposure, Ccl3(-/-)Abca4(-/-)Rdh8(-/-) mice displayed persistent retinal inflammation with appearance of Iba-1(+) cells in the subretinal space, severe photoreceptor cell death, and increased Ccl4 expression compared with Abca4(-/-)Rdh8(-/-) mice. In contrast, Ccl3(-/-)Abca4(-/-)Rdh8(-/-) mice exhibited a milder retinal inflammation and degeneration than Abca4(-/-)Rdh8(-/-) mice did in age-related chronic retinal degeneration under room light conditions. The deficiency of Ccl3 also attenuated the severity of retinal degeneration in Mertk(-/-) mice. Taken together, our results indicate that Ccl3 has an essential role in regulating the severity of retinal inflammation and degeneration in these mouse models.
Insights
Chemokine Ccl3 (macrophage inflammatory protein-1 alpha) drives inflammation and cell death in mouse models of retinal degeneration. Reducing Ccl3 levels lessens disease severity, highlighting its critical role in these conditions.
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- Degenerative retinal diseases often involve inflammatory responses with immune cell infiltration.
- Chemokines play a crucial role in mediating these inflammatory processes.
Purpose of the Study:
- To investigate the role of chemokines, specifically Ccl3 (macrophage inflammatory protein-1 alpha), in mouse models of Stargardt disease and retinitis pigmentosa.
- To determine the impact of Ccl3 deficiency on retinal inflammation and degeneration.
Main Methods:
- Utilized PCR array analysis to identify elevated chemokine expression in Abca4(-/-)Rdh8(-/-) mice after light exposure.
- Generated Ccl3 knockout mouse models (Ccl3(-/-)Abca4(-/-)Rdh8(-/-) and Ccl3(-/-)Mertk(-/-)) to study the in vivo effects of Ccl3 deficiency.
- Assessed retinal inflammation, photoreceptor cell death, and immune cell infiltration in response to light exposure and aging.
Main Results:
- Ccl3 (MIP-1a) expression was significantly elevated in Abca4(-/-)Rdh8(-/-) mice following light exposure.
- Microglia were identified as the primary source of Ccl3 secretion.
- Ccl3 deficiency attenuated retinal inflammation, photoreceptor cell death, and overall degeneration in both acute light-induced and chronic age-related models.
Conclusions:
- Ccl3 is a key mediator of retinal inflammation and degeneration in the studied mouse models.
- Targeting Ccl3 may offer a therapeutic strategy for mitigating vision loss in degenerative retinal diseases.
More Related Videos
12:48In Vivo Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma
Published on: May 11, 2015
06:27Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish
Published on: October 27, 2017