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Published on: August 7, 2015
Meteorin Is a Novel Therapeutic Target for Wet Age-Related Macular Degeneration
Kimberley Delaunay1, Alexandre Sellam1, Virginie Dinet1,2
1Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, INSERM, From Physiopathology of Retinal Diseases to Clinical Advances, 75006 Paris, France.
Abstract:
The aim of this study was to evaluate the potential anti-angiogenic effect of MTRN (meteorin) in the laser-induced CNV rat model and explore its mechanisms of action. MTRN, thrompospondin-1, glial cell markers (GFAP, vimentin), and phalloidin were immuno-stained in non-human primate flat-mounted retinas and human retina cross sections. The effect of MTRN at different doses and time points was evaluated on laser-induced CNV at 14 days using in vivo fluorescein angiography and ex vivo quantification of CNV. A pan transcriptomic analysis of the retina and the RPE/choroid complex was used to explore MTRN effects mechanisms. In human retina, MTRN is enriched in the macula, expressed in and secreted by glial cells, and located in photoreceptor cells, including in nuclear bodies. Intravitreal MTRN administered preventively reduced CNV angiographic scores and CNV size in a dose-dependent manner. The highest dose, administered at day 7, also reduced CNV. MTRN, which is regulated by mineralocorticoid receptor modulators in the rat retina, regulates pathways associated with angiogenesis, oxidative stress, and neuroprotection. MTRN is a potential novel therapeutic candidate protein for wet AMD.
Insights
Meteorin (MTRN) demonstrates anti-angiogenic properties, significantly reducing choroidal neovascularization (CNV) in a rat model. This suggests MTRN is a promising therapeutic candidate for wet age-related macular degeneration (AMD).
Area of Science:
- Ophthalmology
- Molecular Biology
- Regenerative Medicine
Background:
- Choroidal neovascularization (CNV) is a hallmark of wet age-related macular degeneration (AMD), leading to vision loss.
- Identifying novel therapeutic targets for anti-angiogenesis is crucial for treating wet AMD.
- Meteorin (MTRN) is a secreted protein with potential roles in cellular processes.
Purpose of the Study:
- To investigate the anti-angiogenic potential of meteorin (MTRN) in a laser-induced CNV rat model.
- To elucidate the underlying mechanisms of MTRN's action in the retina.
- To assess MTRN as a potential therapeutic candidate for wet AMD.
Main Methods:
- Immunohistochemistry was performed on human and non-human primate retinas to localize MTRN.
- Laser-induced CNV rat model was used to evaluate MTRN's effect on CNV size and vascularization.
- In vivo fluorescein angiography and ex vivo quantification assessed CNV.
- Pan-transcriptomic analysis explored MTRN's mechanism of action.
Main Results:
- MTRN is expressed in human retinal glial cells and photoreceptors, particularly in the macula.
- Intravitreal MTRN administration significantly reduced CNV size and vascularization in a dose-dependent manner.
- MTRN treatment, even when delayed, showed efficacy in reducing CNV.
- Transcriptomic analysis revealed MTRN regulates pathways involved in angiogenesis, oxidative stress, and neuroprotection.
Conclusions:
- Meteorin (MTRN) exhibits significant anti-angiogenic effects in a preclinical model of wet AMD.
- MTRN's mechanism involves modulation of key pathways related to angiogenesis and retinal protection.
- MTRN represents a potential novel therapeutic protein for the treatment of wet age-related macular degeneration.
