RESUMEN
X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.
Asunto(s)
Proteínas del Ojo , Células Madre Pluripotentes Inducidas , Organoides , Retina , Retinosquisis , Humanos , Retinosquisis/genética , Retinosquisis/metabolismo , Retinosquisis/patología , Organoides/metabolismo , Organoides/patología , Células Madre Pluripotentes Inducidas/metabolismo , Masculino , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Retina/metabolismo , Retina/patología , Diferenciación Celular/genética , Modelos BiológicosRESUMEN
PURPOSE: To evaluate the efficacy and safety of vitreoretinal surgery using a 23-gauge transconjunctival sutureless vitrectomy (TSV) system for various vitreoretinal diseases. METHODS: A retrospective, consecutive, interventional case series was performed for 40 eyes of 40 patients. The patients underwent vitreoretinal procedures using the 23-gauge TSV system, including idiopathic epiretinal membrane (n=7), vitreous hemorrhage (n=11), diabetic macular edema (n=10), macular hole (n=5), vitreomacular traction syndrome (n=5), diabetic tractional retinal detachment (n=1), and rhegmatogenous retinal detachment (n=1). Best corrected visual acuity (BCVA), intraocular pressure (IOP), and intra- and post-operative complications were evaluated. RESULTS: Intraoperative suture placement was necessary in 3 eyes (7.5%). The median BCVA improved from 20/400 (LogMAR, 1.21+/-0.63) to 20/140 (LogMAR, 0.83+/-0.48) at 1 week (p=0.003), 20/100 (LogMAR, 0.85+/-0.65) at 1 month (p=0.002), 20/100 (LogMAR, 0.73+/-0.6) at 3 months (p=0.001). In 1 eye, IOP was 5 mmHg at 2 hours and 4 mmHg at 5 hours, but none of the eyes showed hypotony after 1 postoperative day. No serous postoperative complications were observed during a mean follow-up of 8.4+/-3.4 months (range 3-13 months) CONCLUSIONS: The 23-gauge TSV system shows promise as an effective and safe technique for a variety of vitreoretinal procedures. It appears to be a less traumatic, more convenient alternative to 20-gauge vitrectomy in some indications.