Rs1, which encodes retinoschisin, is a key gene in congenital retinoschisis. Retinoschisin is likely involved in maintaining the structural integrity of the retina. The study of Rs1 has been facilitated by gene knockout (KO) mouse models, which are important research models for in-vivo studies to understand its function [1,2,3,4].

In a Rs1-KO mouse model of X-linked retinoschisis (XLRS), AAV2/4-RS1 gene therapy via subretinal or intravitreal injection showed promise in improving the retinal phenotype, with subretinal delivery being superior. Topical brinzolamide did not enhance the efficacy [1]. In another study, intravitreal delivery of rAAV2-hSyn-hRS1 led to retinal ganglion cell-specific gene expression and retinal improvement in the Rs1-KO mouse, supporting the clinical development of this vector for XLRS patients [4]. Additionally, a rat model with targeted deletion of Rs1 exon-1 (Rs1-/Y) exhibited early-onset and rapidly progressive photoreceptor degeneration, and intravitreal AAV8-RS1 at an early stage rescued the inner nuclear layer and outer plexiform layer cavity formation [3].

In conclusion, Rs1 is crucial for normal retinal development and function. The study of Rs1-KO and related models has provided valuable insights into the mechanisms of X-linked retinoschisis and potential gene therapy strategies for this disease. These models have also shown the potential of gene augmentation therapy to rescue the abnormal phenotypes associated with Rs1 deficiency in the retina [1,3,4].

References:

1. Scruggs, Brittni A, Bhattarai, Sajag, Helms, Megan, Baker, Sheila A, Drack, Arlene V. 2022. AAV2/4-RS1 gene therapy in the retinoschisin knockout mouse model of X-linked retinoschisis. In PloS one, 17, e0276298. doi:10.1371/journal.pone.0276298. https://pubmed.ncbi.nlm.nih.gov/36477475/

2. Duan, Chunwen, Ding, Chengcheng, Sun, Xihao, Chen, Jiansu, Tang, Shibo. 2024. Retinal organoids with X-linked retinoschisis RS1 (E72K) mutation exhibit a photoreceptor developmental delay and are rescued by gene augmentation therapy. In Stem cell research & therapy, 15, 152. doi:10.1186/s13287-024-03767-4. https://pubmed.ncbi.nlm.nih.gov/38816767/

3. Ye, Eun-Ah, Zeng, Yong, Thomas, Serafina, Smit-McBride, Zeljka, Sieving, Paul A. 2022. XLRS Rat with Rs1-/Y Exon-1-Del Shows Failure of Early Postnatal Outer Retina Development. In Genes, 13, . doi:10.3390/genes13111995. https://pubmed.ncbi.nlm.nih.gov/36360232/

4. Zheng, Yangyang, Xu, Xin, Fan, Ruoyue, Liu, Ying, Luo, Guangzuo. . Intravitreal Delivery of rAAV2-hSyn-hRS1 Results in Retinal Ganglion Cell-Specific Gene Expression and Retinal Improvement in the Rs1-KO Mouse. In Human gene therapy, 35, 342-354. doi:10.1089/hum.2023.209. https://pubmed.ncbi.nlm.nih.gov/38661546/