Restoring Useful Filed of Vision in Drosophila Using RNAi Knockdown of the eys Gene and Duloxetine Treatment

By Camille Jacome

Faculty Mentor: Dr. Ginny Morriss

Abstract

Retinitis pigmentosa is the gradual degeneration of photoreceptor cells in the retina that causes vision loss over time. Mutations in the eyes shut homolog (eys), a protein coding gene necessary to support the photoreceptor cells, can lead to this condition. Earlier research has shown that Duloxetine, a selective serotonin & norepinephrine reuptake inhibitor (SSNRI) can restore mutated stem cells by inhibiting the MEK/ERK pathway, suggesting it can be repurposed to treat progressive vision loss. To assess changes in visual function and acuity, we analyze useful field of vision (UFOV) which is defined as the visual area where information is collected without turning the head or eye movement. A low UFOV results in poor mobility performance that requires navigation. To mimic this, we used RNAi, which is a technique that modifies gene expression, effectively silencing the eys gene in our model organism Drosophila. We treated flies with Duloxetine in concentrations of 20uM and 30uM over a period of 14 days and monitored their movement towards a visual target to assess improvement in UFOV. We saw that the 30uM treated flies were moving very slowly, but the other groups moved closer to the target with normal movement. A two-way ANOVA analysis was done to see if there was a difference in treatment groups and over time; no statistical significance was found. The goal of this study was to find an effective baseline Duloxetine dosage for possible drug repurposing in human trials.


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