| Autor: |
Ella J. Gehrke, Jacob Thompson, Emily Kalmanek, Sarah T. Stanley, Joseph Laird, Sajag Bhattarai, Brianna Lobeck, Sara Mayer, Angela Mahoney, Salma Hassan, Ying Hsu, Arlene Drack |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Frontiers in Medicine, Vol 11 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2296-858X |
| DOI: |
10.3389/fmed.2024.1302119 |
| Popis: |
IntroductionX-linked retinoschisis (XLRS) is a vitreoretinal dystrophy caused by RS1 gene mutations which disrupt retinoschisin-1 (RS1) function. Vital for retinal architecture, the absence of functional RS1 leads to the development of intraretinal cysts. Intravitreal injection of a gene therapy for treating XLRS caused ocular inflammation in high dose groups in a phase I/II clinical trial. This study investigates a low dose subretinal gene therapy in Rs1 knockout (Rs1-KO) mice compared to injection of buffer alone. Observation of an unexpected therapeutic effect following the subretinal injection of the hypertonic buffer led to novel findings in XLRS.MethodsRs1-KO mice were subretinally injected with an AAV2/4 vector (n = 10) containing the RS1 gene driven by an Ef1α promoter, a hypertonic buffer (n = 15) (180 mM NaCl 0.001% F68/PBS (pH 7.4)), or isotonic buffer (n = 7) (155.2 mM NaCl 0.001% F68/PBS, pH 7.0). A sham puncture group was also included (n = 6). Endpoints included electroretinogram (ERG), optical coherence tomography (OCT), a visually guided swim assay (VGSA), and immunohistochemistry.ResultsUnexpectedly, hypertonic buffer-injected eyes had reduced cyst severity at 1-month post-injection (MPI) (p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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