RESUMEN
Retinitis pigmentosa (RP) is a genetic blinding disease with over 80 causative genes. Disease progression varies between patients with similar genetic backgrounds. We assessed the association between environment, gut microbiota, and retinal degeneration in the RP rat model Royal College of Surgeons (RCS). The rats were born and raised for two generations under specific pathogen-free (SPF, n = 69) or non-SPF conditions (n = 48). At the age of four weeks, SPF rats had significantly shorter dark-adapted a-wave and dark and light-adapted b-wave implicit times by electroretinogram (p = 0.014, p = 9.5*10-6, p = 0.009, respectively). The SPF rats had significantly less photoreceptor apoptosis at ages four, eight, and twelve weeks (all p < 0.022), significantly thicker debris zone at age 14 weeks, and smaller hypofluorescent lesions in SPF rats at ages 10-16 weeks, especially in the inferior retina. The non-SPF rats had significantly higher microbiota alpha diversity (p = 0.037) and failed to present the age-related maturation of Proteobacteria, Spirochaetes, Actinobacteria, and Bacteroidetes seen in SPF conditions. Specific microbial amplicon sequence variants were reduced in rats with more severe retinal degeneration. Our data suggest an environmental effect on retinal deterioration in RCS rats. These findings may lead to the development of novel microbiome-related interventions for retinal degeneration.
Asunto(s)
Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Degeneración Retiniana , Animales , Ratas , Degeneración Retiniana/microbiología , Degeneración Retiniana/patología , Organismos Libres de Patógenos Específicos , Electrorretinografía , Retinitis Pigmentosa/microbiología , Retinitis Pigmentosa/patología , Retina/microbiología , Retina/patología , Vivienda para Animales , MasculinoRESUMEN
Background: Extracorporeal shockwave therapy (ESWT) is a noninvasive treatment modality that is used in the treatment of chronic Achilles tendinopathy (AT). Purposes: To (1) retrospectively assess outcomes after ESWT for both noninsertional AT (NAT) and insertional AT (IAT) at >1-year follow-up and (2) identify potential predictors of outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: Chart review was conducted to identify patients who underwent ESWT for AT with a minimum of 1-year follow-up. Data collected and assessed included patient demographic characteristics, pathological characteristics including the location of AT (NAT or IAT), presence of a Haglund deformity, and severity of tendon degeneration on magnetic resonance imaging (MRI), in addition to treatment characteristics including number of sessions and intensity of ESWT. The Victorian Institute of Sports Assessment-Achilles (VISA-A) and visual analog scale (VAS) pain scores were obtained before ESWT, 6 months after ESWT, and at final follow-up. Failures were also recorded, which were defined as no improvement in VISA-A or VAS scores or need for surgical intervention. Linear regression was performed to identify potential predictors of inferior subjective clinical outcomes and failures. Survival analysis was conducted using Kaplan-Meier curves. Results: The study included 52 patients with IAT and 34 patients with NAT. The mean follow-up in the NAT cohort was 22.3 ± 10.2 months and the mean follow-up in the IAT cohort was 26.8 ± 15.8 months. Improvements in VISA-A and VAS scores were observed in the NAT cohort at 6-month follow-up and at final follow-up (P < .05). Improvements in VISA-A and VAS scores were recorded in the IAT cohort at 6-month follow-up, which subsequently deteriorated at final follow-up. In the NAT cohort, the failure rate at 6-month follow-up was 11.8%, which increased to 29.4% at final follow-up. In the IAT cohort, the failure rate at 6-month follow-up was 32.7%, which increased to 59.6% at final follow-up. Predictors of inferior subjective clinical outcomes and failures in the NAT cohort included pre-ESWT subjective clinical score, male sex, presence of a cardiovascular risk factor, and more severe MRI grading of tendinopathy. Predictors of inferior subjective clinical outcomes and failures in the IAT cohort included pre-ESWT subjective clinical score and more severe MRI grading of tendinopathy. Conclusion: Superior subjective clinical outcomes together with a lower failure rate were maintained for >1 year in the NAT cohort compared with the IAT cohort, calling into question the long-term benefit of ESWT for patients with IAT.