title: Oncostatin M protects rod and cone photoreceptors and promotes regeneration of cone outer segment in a rat model of retinal degeneration.
abstract: Retinitis pigmentosa (RP) is a group of photoreceptor degenerative disorders that lead to loss of vision. Typically, rod photoreceptors degenerate first, resulting in loss of night and peripheral vision. Secondary cone degeneration eventually affects central vision, leading to total blindness. Previous studies have shown that photoreceptors could be protected from degeneration by exogenous neurotrophic factors, including ciliary neurotrophic factor (CNTF), a member of the IL-6 family of cytokines. Using a transgenic rat model of retinal degeneration (the S334-ter rat), we investigated the effects of Oncostatin M (OSM), another member of the IL-6 family of cytokines, on photoreceptor protection. We found that exogenous OSM protects both rod and cone photoreceptors. In addition, OSM promotes regeneration of cone outer segments in early stages of cone degeneration. Further investigation showed that OSM treatment induces STAT3 phosphorylation in Müller cells but not in photoreceptors, suggesting that OSM not directly acts on photoreceptors and that the protective effects of OSM on photoreceptors are mediated by Müller cells. These findings support the therapeutic strategy using members of IL-6 family of cytokines for retinal degenerative disorders. They also provide evidence that activation of the STAT3 pathway in Müller cells promotes photoreceptor survival. Our work highlights the importance of Müller cell-photoreceptor interaction in the retina, which may serve as a model of glia-neuron interaction in general.
authors.affiliation: Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
authors.forename: Xin
authors.initials: X
authors.lastname: Xia
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Li
authors.forename: Deqiang
authors.initials: D
authors.lastname: Huang
authors.forename: Zhengying
authors.initials: Z
authors.lastname: Wang
authors.forename: Lingyu
authors.initials: L
authors.lastname: Luo
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: Lian
authors.initials: L
authors.lastname: Zhao
authors.forename: Rong
authors.initials: R
authors.lastname: Wen
mesh_terms: D000818:Animals; D019610:Cytoprotection / Q000187:drug effects*; D004195:Disease Models, Animal; D006801:Humans; D053683:Oncostatin M / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects*; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000473:pathology*; D012162:Retinal Degeneration / Q000473:pathology*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000473:pathology*; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000473:pathology*; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D053683:Oncostatin M