title: Suppression of microglial activation is neuroprotective in a mouse model of human retinitis pigmentosa.
abstract: Retinitis pigmentosa (RP) is a photoreceptor-degenerative disease caused by various mutations and is characterized by death of rod photoreceptor cell followed by gradual death of cone photoreceptors. The molecular mechanisms that lead to rod and cone death are not yet fully understood. Neuroinflammation contributes to the progression of many chronic neurodegenerative disorders. However, it remains to be determined how microglia contribute to photoreceptor disruption in RP. In this study, we explored the role of microglia as a contributor to photoreceptor degeneration in the rd10 mouse model of RP. First, we demonstrated that microglia activation was an early alteration in RP retinas. Inhibition of microglia activation by minocycline reduced photoreceptor apoptosis and significantly improved retinal structure and function and visual behavior in rd10 mice. Second, we identified that minocycline exerted its neuroprotective effects through both anti-inflammatory and anti-apoptotic mechanisms. Third, we found that Cx3cr1 deficiency dysregulated microglia activation and subsequently resulted in increased photoreceptor vulnerability in rd10 mice, suggesting that the Cx3cl1/Cx3cr1 signaling pathway might protect against microglia neurotoxicity. We concluded that suppression of neuroinflammatory responses could be a potential treatment strategy aimed at improving photoreceptor survival in human RP.
authors.affiliation: Department of Anatomy.
authors.forename: Bo
authors.identifier: http://orcid.org/0000-0003-4183-5939
authors.initials: B
authors.lastname: Peng
authors.affiliation: Department of Anatomy, Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, 510632 Guangzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Anatomy.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, and State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Li Ka Shing Faculty of Medicine, Pokfulam, Hong Kong, and.
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.affiliation: Department of Anatomy.
authors.forename: George L
authors.initials: GL
authors.lastname: Tipoe
authors.affiliation: Department of Anatomy, Department of Ophthalmology, and State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Li Ka Shing Faculty of Medicine, Pokfulam, Hong Kong, and blin@hku.hk.
authors.forename: Bin
authors.initials: B
authors.lastname: Lin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D000073883:CX3C Chemokine Receptor 1; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D009154:Mutation / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology; D019707:Receptors, Chemokine / Q000235:genetics; D012160:Retina / Q000187:drug effects / Q000502:physiology*; D012162:Retinal Degeneration / Q000209:etiology / Q000517:prevention & control*; D012174:Retinitis Pigmentosa / Q000150:complications* / Q000235:genetics
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D011720:Pyrazoles; D019707:Receptors, Chemokine; C115461:SC 560; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517438:Pde6b protein, mouse; D008911:Minocycline
keywords: Cx3cr1; microglia; minocycline; photoreceptor degeneration; rd10 mice