# Using zebrafish as a model system for investigating lens development, aging and cataract.

> **NIH NIH R15** · ASHLAND UNIVERSITY · 2020 · $311,167

## Abstract

The goal of this proposal is to use zebrafish as a model system to identify novel regulators of
ocular lens development and examine how loss of single and combined α-crystallins, small heat
shock proteins important for lens function, affect lens aging and the regulation of lens crystallin
expression. These experiments will produce a better understanding of lens development and
maintenance of lens transparency important for developing treatments to prevent lens opacities,
the leading cause of blindness worldwide. Work in our laboratory has helped make the zebrafish a
powerful model system for studying lens development, function and disease. Undergraduate
students supported by past funding have cloned and characterized three zebrafish α-crystallins
and used CRISPR/Cas9 gene editing to disable each to examine the impact of their loss on early
lens development. Here, we propose in Aim I to use our already produced knockout lines to model
the impact of α-crystallin loss on the maintenance of lens transparency and the gene regulatory
networks that control lens protein expression. This aim will include an integration of transcriptomic
and proteomic analyses, along with anatomical examination of resulting lens phenotypes. We
hypothesize that the resulting lens phenotypes will depend on the specific α-crystallin lost,
providing a novel examination of αB-crystallin function due to the presence of two orthologs in
zebrafish for the single-copy mammalian gene. In Aim II we will use transcriptomic data sets
generated by our collaborators from mouse and zebrafish tissues to identify possible novel
transcription factors (TFs) regulating lens development. We will then efficiently target these TFs
using CRISPR/Cas9 methods that will allow us to screen for lens phenotypes directly in injected
embryos. Mutant TF alleles that disrupt normal lens development will be carried into stable lines to
detail the role they play in establishing and maintaining lens transparency. We expect that these
two aims will efficiently identify novel regulators of lens development and clarify the role of α-
crystallins in maintaining lens transparency. The experiments proposed will provide excellent
training opportunities for undergraduates in a research setting with a strong track record of student
success.

## Key facts

- **NIH application ID:** 10046498
- **Project number:** 2R15EY013535-05A1
- **Recipient organization:** ASHLAND UNIVERSITY
- **Principal Investigator:** Mason Posner
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $311,167
- **Award type:** 2
- **Project period:** 2001-08-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046498

## Citation

> US National Institutes of Health, RePORTER application 10046498, Using zebrafish as a model system for investigating lens development, aging and cataract. (2R15EY013535-05A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10046498. Licensed CC0.

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