Abstract
Purpose :
Refractive error is one of the most common causes of moderate to severe vision impairment, and its prevalence is rapidly increasing. Refractive error significantly increases the risk of retinal damage through glaucoma, retinal detachment and other secondary pathologies. To identify factors related to refractive error, we have compared transcriptomes from myopic and hyperopic zebrafish eye tissues to search for bidirectionally regulated genes. We have identified serpine3 as the most significantly altered gene in bidirectional refractive error. Here we profile the expression and function of Serpine3 to elucidate its role in eye size control and emmetropization.
Methods :
We use RNAseq analysis of lrp2, mfrp and wild-type adult zebrafish sclera/choroid, RPE and retinal samples. Spectral domain-optical coherence tomography was used to measure ocular dimensions in zebrafish. Zebrafish serpine3 was cloned downstream of TurboID-eGFP for overexpression studies.
Results :
We find that serpine3 is highly expressed in zebrafish RPE, as in humans and mice. serpine3 is upregulated in myopic eyes, and downregulated in hyperopic eyes. TurboID-eGFP labeling of serpine3 in the eye at various stages of development will facilitate the identification of its target proteins.
Conclusions :
SERPINE3 is a promising candidate for the phenotypic effects seen in myopia. Assessing its role in the context of genetic refractive error, combined with molecular characterization of its targets, will elucidate its mechanistic function in eye size control.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.