RESUMO
Retinitis pigmentosa (RP) is the most common inherited retinal disease (IRD) and is characterized by photoreceptor degeneration and progressive vision loss. We report 4 patients presenting with RP from 3 unrelated families with variants in TBC1D32, which to date has never been associated with an IRD. To validate TBC1D32 as a putative RP causative gene, we combined Xenopus in vivo approaches and human induced pluripotent stem cell-derived (iPSC-derived) retinal models. Our data showed that TBC1D32 was expressed during retinal development and that it played an important role in retinal pigment epithelium (RPE) differentiation. Furthermore, we identified a role for TBC1D32 in ciliogenesis of the RPE. We demonstrated elongated ciliary defects that resulted in disrupted apical tight junctions, loss of functionality (delayed retinoid cycling and altered secretion balance), and the onset of an epithelial-mesenchymal transition-like phenotype. Last, our results suggested photoreceptor differentiation defects, including connecting cilium anomalies, that resulted in impaired trafficking to the outer segment in cones and rods in TBC1D32 iPSC-derived retinal organoids. Overall, our data highlight a critical role for TBC1D32 in the retina and demonstrate that TBC1D32 mutations lead to RP. We thus identify TBC1D32 as an IRD-causative gene.
Assuntos
Células-Tronco Pluripotentes Induzidas , Degeneração Retiniana , Retinose Pigmentar , Humanos , Retina , Retinose Pigmentar/genética , Degeneração Retiniana/genética , Epitélio Pigmentado da Retina , Proteínas Adaptadoras de Transdução de SinalRESUMO
PURPOSE: To investigate the etiologies of metamorphopsia after successful retinal detachment repair. METHODS: In this retrospective study, we included patients who underwent pars plana vitrectomy (PPV) for macula-off rhegmatogenous retinal detachment (RRD). Patients were reviewed after 3 to 6 weeks. Best-corrected visual acuity (BCVA), fundus biomicroscopy, Amsler grid test, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence images (FAF) were obtained from all patients to visualize abnormalities in retinal layers and retinal rotation. RESULTS: A total of 50 eyes from 49 consecutive patients were included, of whom 12 (24%) complained of postoperative metamorphopsia. The main cause of metamorphopsia was retinal shift after RRD repair (p < 0.001). CONCLUSION: Distorted vision after macula-off RRD is a common and retinal shift was found to be the main reason patients experience metamorphopsia after a successful macula-off RRD repair.
Assuntos
Angiofluoresceinografia/métodos , Complicações Pós-Operatórias , Retina/diagnóstico por imagem , Descolamento Retiniano/cirurgia , Tomografia de Coerência Óptica/métodos , Transtornos da Visão/diagnóstico , Vitrectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Tamponamento Interno/métodos , Feminino , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Descolamento Retiniano/diagnóstico , Estudos Retrospectivos , Transtornos da Visão/etiologia , Acuidade VisualRESUMO
PURPOSE: To investigate the outcome after combined phaco-vitrectomy in rhegmatogenous retinal detachment (RRD) repair. PATIENTS AND METHODS: In this retrospective study, we included all patients who underwent pars plana vitrectomy (PPV) for RRD between January 2013 and December 2017. The main outcome measure was the retinal re-detachment rate after combined phaco-vitrectomy. RESULTS: Overall, 1017 eyes with RRD were included. All eyes received PPV, while in 516 eyes additional phacoemulsification was performed. A retinal re-detachment occurred in 103 patients (10.1%). No significant difference in the rate of re-detachment was found if additional phacoemulsification was performed (p=0.641). Subgroup calculations showed a significant higher rate of re-detachment in patients with a PVR (p=0.0003) and in patients where silicone oil was used as primary tamponade (p=0.0001) as well as in macula off RRDs (p=0.034). CONCLUSION: Additional phacoemulsification during vitrectomy for RRD is not associated with higher rate of retinal re-detachment.