AUTHOR=Liu Meng , Liu Jingyang , Wang Weiping , Liu Guangming , Jin Xiuxiu , Lei Bo 

TITLE=Longitudinal Photoreceptor Phenotype Observation and Therapeutic Evaluation of a Carbonic Anhydrase Inhibitor in a X-Linked Retinoschisis Mouse Model

JOURNAL=Frontiers in Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.886947

DOI=10.3389/fmed.2022.886947

ISSN=2296-858X

ABSTRACT=<sec><title>Purpose</title><p>To study the long-term photoreceptor changes and to evaluate the effects of topical application of a carbonic anhydrase inhibitor (CAI) in a mouse model of X-linked retinoschisis (XLRS).</p></sec><sec><title>Methods</title><p>Conventional electroretinograms (ERGs) and dark-adapted 10-Hz flicker ERGs were recorded in control and <italic>Rs1</italic><sup>−/<italic>Y</italic></sup> mice generated with CRISPR/Cas9. ON-pathway blocker 2-amino-4-phosphobutyric acid (APB) was injected intravitreally. Morphology was evaluated with histology and optical coherence tomography (OCT). Mice were treated with a CAI inhibitor brinzolamide eye drops (10 mg/ml) three times a day for 3 months. OCT and ERG findings at 1, 4, and 10 months were analyzed.</p></sec><sec><title>Results</title><p>Negative ERGs and retinal cavities were evident in <italic>Rs1</italic><sup>−/<italic>Y</italic></sup> mice. Both a-wave and b-wave amplitudes decreased with age when compared with age-matched controls. The APB-isolated a-wave (a′) amplitudes of <italic>Rs1</italic><sup>−/<italic>Y</italic></sup> mice were reduced in all age groups. In dark-adapted 10-Hz flicker ERG, the amplitude-intensity curve of <italic>Rs1</italic><sup>−/<italic>Y</italic></sup> mice shifted down. The thickness of ONL and IS/OS decreased in <italic>Rs1</italic><sup>−/<italic>Y</italic></sup> mice. CAI reduced the splitting retinal cavities but didn't affect the ERG.</p></sec><sec><title>Conclusions</title><p>In addition to post receptoral impairments, photoreceptor cells underwent progressive dysfunction since early age in <italic>Rs1</italic><sup>−/<italic>Y</italic></sup> mice. Long-term CAI treatment improved the shrinkage of the splitting retinal cavity, while no functional improvement was observed.</p></sec>