Ygal Rotenstreich

Jan 7, 2025 | nature.com | Francesco Parmeggiani |Dominique Brémond-Gignac |Avril Daly |Tom Denee |Marjolein Lahaye |Andrew Lotery | +9 more

X-linked retinitis pigmentosa (XLRP) is considered one of the most severe forms of retinitis pigmentosa (RP), accounting for 5–15% of all RP cases and primarily affecting males. However, the real-world humanistic impacts of this disease on patients are poorly investigated, especially with respect to burdens faced by patients with varying disease severities. EXPLORE XLRP-2 was an exploratory, multicentre, non-interventional study. A retrospective chart review was conducted to collect clinical/demographic data, including XLRP clinical stage (mild, moderate or severe). Cross-sectional surveys were used to gather experiences directly from patients by validated and modified patient-reported outcomes. 176 patients with XLRP caused by retinitis pigmentosa GTPase regulator (RPGR) gene mutation were enrolled, of whom 169 were included in analyses. 81% of patients were male, mean (SD) age was 39.3 (17.61) years, and 20 adolescents were included. Mean age (SD) at genetic confirmation was 33.4 years (17.98), and the mean duration (SD) from initial symptoms to genetic diagnosis was 16.4 (15.66) years. Compared with patients with mild disease, patients with severe XLRP are more likely to experience difficulties with functioning in low luminance, depression, unemployment, productivity issues, mobility and daily activities. This is the first real-world study to collect data directly from patients on the burden of XLRP and to correlate that burden with disease stage. As a result, several areas of significant burden, especially for patients with severe disease, have been identified that should provide focus for future public policies and therapeutic prospects.

Sep 16, 2024 | nature.com | Ifat Sher |Rotem Hadar |Amnon Amir |Yael Haberman |Ygal Rotenstreich |Gali Altmann | +9 more

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.