Relation of response to treatment with dorzolamide in X-linked retinoschisis to the mechanism of functional loss in retinoschisin

Abstract

Purpose: To determine if a positive response of macular cysts to treatment with dorzolamide eye drops in patients with juvenile X-linked retinoschisis (XLRS) can occur with mutations that result in different types of retinoschisin protein dysfunction.

Design: Retrospective case series.

Methods: Thirteen eyes of seven patients seen at the University of Illinois at Chicago with a known diagnosis of XLRS were included. Each patient had received or currently was receiving treatment with topical dorzolamide. One patient from each family was screened for a genetic mutation. Using the method of cell transfection and protein preparation, the mutation in each patient was analyzed further and was categorized into one of three groups: 1) total absence of retinoschisin protein secretion, 2) decreased expression of the secreted protein, or 3) secretion of a nonfunctional protein. The response to dorzolamide was observed using optical coherence tomography.

Results: Significant improvement in the foveal zone thickness was observed with the use of dorzolamide in three of four patients with absence of protein secretion, in two patients with a lack of protein expression, and in one patient with a nonfunctional protein secretion.

Conclusions: This study showed that the response of macular cysts to dorzolamide in patients with XLRS may be observed independent of the mechanism responsible for retinoschisin protein dysfunction. Hence, treatment with dorzolamide may be effective in patients with different mechanisms of dysfunction in retinoschisin.

Trial registration: ClinicalTrials.gov NCT00716586.

Figures

Fig 1

Expression and secretion of wild-type (WT) and G70S (Gly70Ser) mutant retinoschisin. Cells expressing WT or mutant retinoschisin were separated into the cellular (cells) and secreted fraction (medium). The expressed proteins were run on 10% SDS–polyacrylamide gels under reducing conditions. Western blots were labeled with the RS1 3R10 monoclonal antibody. In contrast to WT retinoschisin, the G70S mutant was not present in the secreted fraction