Investigating the role of Myo/Nog cells in proliferative vitreoretinopathy
Location
Philadelphia, PA
Start Date
11-5-2022 1:00 PM
End Date
11-5-2022 4:00 PM
Description
Introduction: Myo/Nog cells are found in many adult tissues including the retina. They express the MyoD transcription factor, bone morphogenetic protein inhibitor Noggin and brain-specific angiogenesis inhibitor 1 (BAI1). It has been demonstrated that Myo/Nog are activated in response to stress and injury, migrate to wounds and differentiate into myofibroblasts that synthesize contractile proteins. After cataract surgery, Myo/Nog cells populate and deform the posterior lens capsule in a vision impairing disease called posterior capsule opacification (PCO) or secondary cataract. Myo/Nog cells also are present in membranes that form on the surface of the human retina in a condition called proliferative vitreoretinopathy (PVR) which occurs after retinal trauma or repair of a retinal detachment. Contractions of epiretinal membranes may lead to re-detachment of the retina and blindness.
Objective: In this study we examined the behavior of Myo/Nog cells in a mouse model of PVR and their contributions to the progression of PVR and retinal detachment.
Methods: PVR was induced in the mouse by injecting human retinal pigment epithelial cells into the vitreous. PVR was graded as 1-6 by fundus imaging, optical coherence tomography and histology. Immunofluorescence was used to view the presence of Myo/Nog cells using a confocal and epifluorescence microscope. Antibodies to BAI1, Noggin, ɑ-smooth muscle actin (ɑ-SMA), and striated myosin heavy chain were used to identify Myo/Nog cells and examine their expression of markers of muscle proteins using a double label procedure.
Results: Retinas with greater PVR progression have numerous Myo/Nog cells marked by BAI1 and Noggin expression. Higher grade epiretinal membranes correlate to higher numbers of Myo/Nog cells which also express ɑ-SMA myosin. The presence of Myo/Nog cells in the PVR membrane was associated with retinal folding and retinal detachment.
Conclusion: Injection of human RPE cells induces activation and expansion of the population of Myo/Nog cells. Their expression in the PVR membrane of myosin and smooth muscle actin in epiretinal membranes and their association with folds strongly suggest that their contractions lead to PVR progression and retinal detachment. Targeted elimination of Myo/Nog cells could potentially prevent re-detachment of the retina and preserve visual acuity.
Embargo Period
5-25-2022
Investigating the role of Myo/Nog cells in proliferative vitreoretinopathy
Philadelphia, PA
Introduction: Myo/Nog cells are found in many adult tissues including the retina. They express the MyoD transcription factor, bone morphogenetic protein inhibitor Noggin and brain-specific angiogenesis inhibitor 1 (BAI1). It has been demonstrated that Myo/Nog are activated in response to stress and injury, migrate to wounds and differentiate into myofibroblasts that synthesize contractile proteins. After cataract surgery, Myo/Nog cells populate and deform the posterior lens capsule in a vision impairing disease called posterior capsule opacification (PCO) or secondary cataract. Myo/Nog cells also are present in membranes that form on the surface of the human retina in a condition called proliferative vitreoretinopathy (PVR) which occurs after retinal trauma or repair of a retinal detachment. Contractions of epiretinal membranes may lead to re-detachment of the retina and blindness.
Objective: In this study we examined the behavior of Myo/Nog cells in a mouse model of PVR and their contributions to the progression of PVR and retinal detachment.
Methods: PVR was induced in the mouse by injecting human retinal pigment epithelial cells into the vitreous. PVR was graded as 1-6 by fundus imaging, optical coherence tomography and histology. Immunofluorescence was used to view the presence of Myo/Nog cells using a confocal and epifluorescence microscope. Antibodies to BAI1, Noggin, ɑ-smooth muscle actin (ɑ-SMA), and striated myosin heavy chain were used to identify Myo/Nog cells and examine their expression of markers of muscle proteins using a double label procedure.
Results: Retinas with greater PVR progression have numerous Myo/Nog cells marked by BAI1 and Noggin expression. Higher grade epiretinal membranes correlate to higher numbers of Myo/Nog cells which also express ɑ-SMA myosin. The presence of Myo/Nog cells in the PVR membrane was associated with retinal folding and retinal detachment.
Conclusion: Injection of human RPE cells induces activation and expansion of the population of Myo/Nog cells. Their expression in the PVR membrane of myosin and smooth muscle actin in epiretinal membranes and their association with folds strongly suggest that their contractions lead to PVR progression and retinal detachment. Targeted elimination of Myo/Nog cells could potentially prevent re-detachment of the retina and preserve visual acuity.
Comments
Winner of PCOM PA CCDA Excellence in Research Award