Retinal Structure and Gene Therapy Outcome in Retinoschisin-Deficient Mice Assessed by Spectral-Domain Optical...

Area of Science:

• Ophthalmology
• Retinal imaging
• Gene therapy

Background:

• X-linked retinoschisis (XLRS) is a genetic disorder causing vision loss.
• Mouse models are crucial for studying XLRS and testing therapies.
• Spectral-domain optical coherence tomography (SD-OCT) offers noninvasive retinal imaging.

Purpose of the Study:

• To characterize the retinal phenotype and disease progression in a mouse model of X-linked retinoschisis (Rs1-KO) using SD-OCT.
• To evaluate treatment responses to AAV8-mediated gene therapy (AAV8-RS1) in Rs1-KO mice.
• To identify novel structural markers for assessing gene therapy outcomes.

Main Methods:

• SD-OCT imaging of wild-type and Rs1-KO mouse retinas from 1 to 12 months.
• Intravitreal injection of AAV8-RS1 in Rs1-KO mice.
• Measurement of retinal cavities, photoreceptor outer nuclear layer (ONL) thickness, and outer retina reflective band (ORRB) morphology.
• Comparison of ORRB morphology with immunohistochemistry and electron microscopy.

Main Results:

• Rs1-KO mice exhibited increasing retinal cavities and decreasing ONL thickness with age.
• ORRB fragmentation and merging patterns were observed in Rs1-KO mice.
• AAV8-RS1 treatment normalized ORRB morphology, correlating with OLM and IS mitochondria recovery.

Conclusions:

• SD-OCT is a sensitive tool for monitoring retinal changes and therapy effects in mouse models.
• ORRB morphology changes can serve as biomarkers for gene therapy efficacy in X-linked retinoschisis.