RESUMO
Animal models of X-linked juvenile retinoschisis (XLRS) are valuable tools for understanding basic biochemical function of retinoschisin (RS1) protein and to investigate outcomes of preclinical efficacy and toxicity studies. In order to work with an eye larger than mouse, we generated and characterized an Rs1h-/y knockout rat model created by removing exon 3. This rat model expresses no normal RS1 protein. The model shares features of an early onset and more severe phenotype of human XLRS. The morphologic pathology includes schisis cavities at postnatal day 15 (p15), photoreceptors that are misplaced into the subretinal space and OPL, and a reduction of photoreceptor cell numbers by p21. By 6 mo age only 1-3 rows of photoreceptors nuclei remain, and the inner/outer segment layers and the OPL shows major changes. Electroretinogram recordings show functional loss with considerable reduction of both the a-wave and b-wave by p28, indicating early age loss and dysfunction of photoreceptors. The ratio of b-/a-wave amplitudes indicates impaired synaptic transmission to bipolar cells in addition. Supplementing the Rs1h-/y exon3-del retina with normal human RS1 protein using AAV8-RS1 delivery improved the retinal structure. This Rs1h-/y rat model provides a further tool to explore underlying mechanisms of XLRS pathology and to evaluate therapeutic intervention for the XLRS condition.
Assuntos
Moléculas de Adesão Celular , Proteínas do Olho , Retinosquise , Animais , Moléculas de Adesão Celular/genética , Suplementos Nutricionais , Eletrorretinografia , Éxons/genética , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Humanos , Fenótipo , Ratos , Retina/metabolismo , Retinosquise/genética , Retinosquise/patologia , Retinosquise/terapiaRESUMO
In this study a new original technique is proposed for treatment of II-III retinoschisis using diode laser Milon Lachta (Saint-Petersburg). Laser radiation parameters were wave length 0,83 microm, energy 350-850 m W, time 0,2-0,3 s, spot diameter 150-200 microm. Original technique of gradual progressive laser coagulation was performed in 72 patients with II-I1 retinoschisis using diode laser. This treatment allowed to preserve macular function to the maximum.