# Mechanisms of development of curved refractive surfaces

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $410,000

## Abstract

Abnormal curvature of the cornea is associated with multiple visual defects including myopia,
hyperopia, keratoconus and astigmatism. However, the developmental mechanisms that generate
appropriate corneal curvature are not well understood. This proposal will use the Drosophila corneal lens as
a simple model system to investigate the development of curvature, and will test whether it shares common
molecular and developmental mechanisms with the mammalian cornea. The project is based on data
showing that the conserved Blimp-1 transcription factor is essential for external curvature of the Drosophila
corneal lens, and that it acts in the peripheral secondary and tertiary pigment cells rather than in the central
cells that secrete the bulk of the extracellular corneal lens material. The possibility of an analogous function
for mouse Blimp1/Prdm1 is suggested by its enrichment in the limbal epithelial cells at the periphery of the
adult cornea. The first aim will investigate the transcriptional network that controls Drosophila corneal lens
development. In the absence of Blimp-1, the C/EBP homologue Slow border cells (Slbo) is highly
upregulated, and Slbo overexpression, like loss of Blimp-1, results in externally flat corneal lenses. The
hypothesis that slbo repression is a major function of Blimp-1 will be tested by inactivating both genes
simultaneously. This aim will also identify other critical transcription factors downstream of Blimp-1, and will
test whether transient hormonally regulated expression of Blimp-1 in the eye is important for the temporal
control of differentiation. The second aim will determine how the peripheral pigment cells contribute to
corneal lens curvature. Two possibilities will be investigated: that pigment cells secrete protein components
that localize to the peripheral corneal lens and give it structural properties distinct from the central region,
and that force exerted on the corneal lens through its attachments to pigment cells controls the pattern of
curvature. The third aim will explore possible conservation between insect and mammalian corneal
structures. CG43333, a gene that is repressed by Blimp-1 in the Drosophila retina and contributes to the
abnormal corneal lens phenotype of Blimp-1 mutants, is homologous to Transforming growth factor beta-
induced protein, a frequent target of mutation in human corneal dystrophies. The effect of disease mutations
on CG43333 accumulation and localization will be examined to determine whether they reproduce features
of corneal dystrophy. Human corneal epithelial cells and corneal organoids will be used to establish whether
human BLIMP1 has target genes in common with Drosophila Blimp-1 in the cornea. Finally, the
developmental expression pattern of Blimp1 in the mouse cornea will be examined to determine whether it
is consistent with a role in corneal curvature. These experiments will elucidate how curvature is imparted to
refractive structures composed primarily of extracellu...

## Key facts

- **NIH application ID:** 10443019
- **Project number:** 1R01EY032896-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jessica E Treisman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $410,000
- **Award type:** 1
- **Project period:** 2022-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10443019

## Citation

> US National Institutes of Health, RePORTER application 10443019, Mechanisms of development of curved refractive surfaces (1R01EY032896-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10443019. Licensed CC0.

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