minocycline and Retinal-Detachment

Retinal detachment (RD) is a severe sight-threatening complication that can be caused by a multitude of retinal diseases. It has been evidenced that minocycline exerts neuroprotective effects by targeting microglia in the pathogenesis of massive ocular lesions including RD, but mechanisms remain elusive. We carried out this research to elucidate the potential mediators that link RD-induced vision loss with microglia reactivity by discussing effects of minocycline on cytokine levels and A20, a negative regulator of inflammation. Minocycline or vehicle was intraperitoneally administrated immediately after RD and continued daily before animals being euthanized. The oxygen glucose deprivation assay was undertaken on the co-cultured BV-2 and 661W cells to mimic the condition of RD in vitro, where A20 siRNA was adopted to knock down the A20 expression in BV-2 cells. Photoreceptor cells apoptosis, inflammatory response and microglia activity following RD with or without minocycline were evaluated. Photoreceptor cells apoptosis and inflammatory response were induced after RD, which could be largely counteracted by minocycline. Minocycline postponed the migration and proliferation of microglia and facilitated their transition to the M2 subtype following RD. Blocking A20 expression in BV-2 cells with siRNA crippled the effect of minocycline. Collectively, minocycline yields a promoting effect on photoreceptor cells survival post-RD by modulating the transformation of microglia phenotypes, in which process A20 may play a "bridge" role.

Topics: Animals; Anti-Bacterial Agents; Blotting, Western; Coculture Techniques; Disease Models, Animal; Gene Expression Regulation; In Situ Nick-End Labeling; Inflammation; Male; Mice; Mice, Inbred C57BL; Microglia; Minocycline; NLR Family, Pyrin Domain-Containing 3 Protein; Phenotype; Photoreceptor Cells; Real-Time Polymerase Chain Reaction; Retinal Detachment; RNA, Messenger; Transfection; Tumor Necrosis Factor alpha-Induced Protein 3

This is a report of an 80-year-old man with a history of rosacea and rhinophyma treated for 15 years with oral minocycline who developed significant minocycline-induced hyperpigmentation. He also had a history of Fuchs' endothelial dystrophy and had undergone penetrating keratoplasty in the right eye. Best-corrected visual acuity was 20/60 in both eyes. Examination revealed slate-grey hyperpigmentation of his body, face, and sclera and black, confluent pigmentation in the central maculae of both eyes. Green wavelength fundus autofluorescence demonstrated speckled hyperautofluorescence in the right eye, and swept-source OCT and OCTA demonstrated pigmented epithelial detachments and significant signal blocking without choroidal neovascularization.

Topics: Administration, Oral; Aged, 80 and over; Anti-Bacterial Agents; Fluorescein Angiography; Humans; Hyperpigmentation; Male; Minocycline; Multimodal Imaging; Optical Imaging; Prospective Studies; Retinal Detachment; Retinal Pigment Epithelium; Rhinophyma; Rosacea; Tomography, Optical Coherence

To determine whether systemic minocycline can protect photoreceptors in experimental retinal detachment (RD).. Retinal detachment was induced in mice by subretinal injection of sodium hyaluronate, 1.4%. In 1 experiment, mice received daily injections of minocycline (group 1) or saline (group 2). In a second experiment, mice were treated with minocycline or saline beginning 24 hours prior, immediately after, or 24 hours after experimental RD. In both experiments, photoreceptor cell survival and apoptosis were assessed by immunohistochemistry with primary antibodies against photoreceptor cell markers, rod rhodopsin, and cone opsin, and by terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling.. Photoreceptor cell apoptosis was detected at day 1 after experimental RD, with apoptotic cells peaking in number at day 3 and dropping by day 7. Treatment with minocycline significantly reduced the number of apoptotic photoreceptor cells associated with RD when given 24 hours before or even 24 hours after RD.. Our data suggest that minocycline may be useful in the treatment of photoreceptor degeneration associated with RD, even when given up to 24 hours after RD.. Use of minocycline in patients with macula-off RD may prevent photoreceptor apoptosis and glial cell proliferation, improving final visual outcomes.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Caspase 3; Cell Survival; Disease Models, Animal; Fluorescent Antibody Technique, Indirect; Glial Fibrillary Acidic Protein; In Situ Nick-End Labeling; Mice; Mice, Inbred C57BL; Minocycline; Monocytes; Opsins; Photoreceptor Cells, Vertebrate; Retinal Degeneration; Retinal Detachment; Rhodopsin