Modulation of Systemic Osmolarity Alters Retinal Thickness and Schisis Cavities Without Blood Retinal Barrier Disruption in Rs1 Knockout Mice.

Purpose: The purpose of this study was to determine whether systemic osmolarity modulation through dehydration or hydration alters retinal thickness and schisis cavity area in Rs1 knockout (KO) mice compared with wild-type (WT) controls, and whether such changes occur without disruption of the blood-retinal barrier (BRB). Methods: Postnatal day 30 Rs1 KO and WT mice underwent dehydration (dry anesthesia) or hydration (intraperitoneal injection of distilled water, 40 mL/kg) during in vivo optical coherence tomography (OCT) imaging. Retinal thickness and schisis cavity area were quantified from serial OCT B-scans. BRB integrity was evaluated using fluorescein angiography (FA) and immunostaining of retinal and retinal pigment epithelium (RPE) junctional markers. Results: Dehydration significantly reduced retinal thickness and schisis cavity area in Rs1 KO mice, with changes of greater magnitude than those observed in WT controls. Hydration increased retinal thickness in WT mice, whereas Rs1 KO mice had a relatively blunted and variable structural response compared to WT in both retinal thickness and schisis cavity area. FA and immunostaining revealed no evidence of vascular leakage or RPE junctional disruption in either genotype, indicating preserved BRB integrity under all experimental conditions. Conclusions: These results demonstrate that systemic osmolarity modulation alters retinal structure in X-linked retinoschisis (XLRS) through mechanisms independent of BRB disruption. The exaggerated response to dehydration and attenuated response to hydration in Rs1 KO suggest altered intraretinal fluid dynamics and biomechanical constraints associated with schisis cavities. These findings indicate that modulation of osmolarity may represent a potential therapeutic approach for intraretinal fluid accumulation in XLRS.